Category Archives: Gene therapy

Alliance for Gene Cancer Therapy Executive Director Margaret C. Cianci and President and CEO John E. Walter outside the nonprofits headquarters in Stamford. Photo by Phil Hall.

The development of an experimental gene-targeting therapy in cancer treatment that could be approved for the U.S. market this year was sparked in large part by the research funding support of a Stamford nonprofit.

The chimeric antigen receptor T-cell (CAR-T) drug, labeled tisagenlecleucel by its manufacturer, Novartis, in July was unanimously recommended for approval by the oncologic drugs advisory committee of the U.S. Food and Drug Administration. If the FDA grants final approval as expected this fall, it will be the first drug treatment targeting human genes approved for the U.S. market.

In Stamford, the Alliance for Cancer Gene Therapy since 2004 has provided a total of $1.8 million to Dr. Carl June at the University of Pennsylvania, the lead researcher in developing the CAR-T therapy. John E. Walter, president and CEO of the Stamford organization, said Junes work has helped to redefine perceptions of what gene therapy can accomplish.

Oftentimes, gene therapy is perceived as taking the bad genes out and putting some good genes in, Walter said. In this case, a patients T-cells are being removed and re-engineered with a virus and reintroduced in the body. With this genetic re-engineering, they become killer T-cells they go in and go after and kill the cancer cells.

Cancer cells in your body multiply and dont know how to die, said Alliance for Gene Cancer Therapy Executive Director Margaret C. Cianci. We have cells in our system all of the time that are growing and dying, but cancer cells dont do that. This therapy is for supercharging your own immune system to recognize these cancer cells and kill them.

If approved, the Novartis drug would mark a milestone achievement for the Alliance, whose creation in 2001 was driven by a tragic loss caused by cancer in its co-founders family. Edward Netter, chairman and CEO of Geneve Corp., a financial services holding company in Stamford, and his wife Barbara, a staff therapist at Pelham Family Services in Westchester County, lost their daughter-in-law, Kimberly Lawrence-Netter, to breast cancer. Edward Netter died from cancer in 2011. His wife serves as the nonprofits honorary board chairwoman.

Walter, who served as CEO of the Leukemia & Lymphoma Society before joining the Alliance in May 2016, noted that this organization differed from most because all of its raised funds are used solely to finance research. Our administrative expenses are paid for by our board and by the Netters, he said, and the nonprofits four-person staff works out of Geneve Corp. headquarters. One hundred percent of your contributions go to research.

Since its founding, the Alliance has allocated approximately $29 million in grants to U.S. and Canadian projects. These are grants to two different types of scientists, said Cianci. We started funding young investigators at assistant professor level who have just become independent. It is difficult for them to get funding, especially in an area as innovative as gene therapy, and the government doesnt like to fund what they see as high-risk projects. We also fund clinical investigators, which included Dr. June.

The Alliance puts out two requests for funding applications each year, which are judged through a peer-review process coordinated by a scientific advisory committee.

There is always more research than there are dollars, said Walter. Invariably, we are leaving research on the table because we dont have the dollars to fund those.

The nonprofit itself receives funding through contributions from longtime donors and an annual fundraising event coordinated by Swim Across America that is held in the Long Island Sound directly across from its offices. That raises about $400,000 a year, Walter said.

Dr. Junes Alliance-funded research was published in a medical journal in 2011 in a study of three patients with advanced chronic lymphocytic leukemia. Novartis, the Swiss pharmaceutical company, expressed interest in the results and paid the University of Pennsylvania $20 million to license the technology.

Once we have survival data for these patients in Novartis-sponsored clinical trials, over time the FDA could consider using this as frontline treatment instead of highly toxic chemotherapy, said Walter.

For Cianci, the Alliances mission is crucial in encouraging new generations of researchers to focus on cancer and gene therapy solutions, especially when federal funding is being threatened by budget cuts.

If we dont fund the young scientists, they are going to leave the field, she warned. We dont want to lose some of these incredible minds. The average age for getting your first grant from the National Institute of Health is 42. What do you tell someone who just became a postdoctoral researcher and wants to have their own lab? How are they going to get funding?

One in four people could potentially get cancer in their lifetimes, Cianci said. And who hasnt been touched by cancer in one way or another?

Follow this link:
Alliance for Gene Cancer Therapy funded pioneering cancer treatment research - Westfair Online

Agilis Biotherapeutics has formed a joint venture with Japans Gene Therapy Research Institution (GTRI). The alliance gives Agilis a base in Japan and a partnership with a fellow CNS specialist to support its development of adeno-associated virus (AAV) vectors and gene therapies.

Cambridge, Massachusetts-based Agilis set up the joint venture using a grant from the Japanese government. The agreement will establish an AAV manufacturing facility in Japan, from where Agilis and GTRI will work on vectors using Sf9 baculovirus and HEK293 mammalian cell systems. Agilis and GTRI plan to develop and manufacture AAV gene therapy vectors through the joint venture.

Agilis and GTRI also plan is to collaborate on the development and commercialization of certain CNS gene therapies.

GTRIs background suggests it is well-equipped to contribute to the project. The Japanese company grew out of the work of Shin-ichi Muramatsu, M.D., a scientist who sequenced AAV3 in the 1990s before going on to create AAVs designed to cross the blood-brain barrier. GTRI is working on gene therapies against diseases including Alzheimers, amyotrophic lateral sclerosis and Parkinsons that build on this research into AAVs.

Both biotechs are developing gene therapies to treat aromatic l-amino acid decarboxylase (AADC) deficiency. GTRI aims to get its candidate into the clinic in 2019. Agilispicked up its candidate from a university in Taiwan, which enrolled 18 patients in two clinical trials of the gene therapy. Those trials have taken the candidate toward a pivotal trial.

These programs may benefit from the joint venture. Working out of the Life Science Innovation Center of Kawasaki City, the joint venture intends to develop and produce AAVs for use in gene therapies against AADC deficiency and Parkinson's.

The joint venture marks the second time Agilis has looked outside of its walls for help with AAV vectors. Late in 2013, Agilis struck a deal with Intrexon that gave it access to the latters vector platform. Agilis is using the vectors to develop a treatment for Friedreichs ataxia.

Read the original:
Agilis forms joint venture to advance gene therapy vectors - FierceBiotech

Weve always said in the past gene editing shouldnt be done, mostly because it couldnt be done safely, said Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology who co-led the committee. Thats still true, but now it looks like its going to be done safely soon, he said, adding that the research is a big breakthrough.

What our report said was, once the technical hurdles are cleared, then there will be societal issues that have to be considered and discussions that are going to have to happen. Nows the time.

Scientists at Oregon Health and Science University, with colleagues in California, China and South Korea, reported that they repaired dozens of embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.

If embryos with the repaired mutation were allowed to develop into babies, they would not only be disease-free but also would not transmit the disease to descendants.

The researchers averted two important safety problems: They produced embryos in which all cells not just some were mutation-free, and they avoided creating unwanted extra mutations.

It feels a bit like a one small step for (hu)mans, one giant leap for (hu)mankind moment, Jennifer Doudna, a biochemist who helped discover the gene-editing method used, called CRISPR-Cas9, said in an email.

Scientists tried two techniques to remove a dangerous mutation. In the first, genetic scissors were inserted into fertilized eggs. The mutation was repaired in some of the resulting embryos but not always in every cell. The second method worked better: By injecting the scissors along with the sperm into the egg, more embryos emerged with repaired genes in every cell.

When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.

Gene-editing

components inserted

after fertilization

Cell with

unrepaired

gene

Mosaicism in

later-stage embryo

When gene-editing components were introduced with sperm to the egg before fertilization, more embryos had repaired mutations in every cell.

Gene-editing components

inserted together with sperm,

before fertilization

In 42 of 58

embryos

tested, all

cells were

repaired

Uniform

later-stage embryo

When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.

Gene-editing

components inserted

after fertilization

Cell with

unrepaired

gene

Mosaicism in

later-stage embryo

When gene-editing components were introduced with sperm to the egg before fertilization, more embryos had repaired mutations in every cell.

Gene-editing

components inserted

together with sperm,

before fertilization

In 42 of 58

embryos

tested, all

cells were

repaired

Uniform

later-stage embryo

I expect these results will be encouraging to those who hope to use human embryo editing for either research or eventual clinical purposes, said Dr. Doudna, who was not involved in the study.

Much more research is needed before the method could be tested in clinical trials, currently impermissible under federal law. But if the technique is found to work safely with this and other mutations, it might help some couples who could not otherwise have healthy children.

Potentially, it could apply to any of more than 10,000 conditions caused by specific inherited mutations. Researchers and experts said those might include breast and ovarian cancer linked to BRCA mutations, as well as diseases like Huntingtons, Tay-Sachs, beta thalassemia, and even sickle cell anemia, cystic fibrosis or some cases of early-onset Alzheimers.

You could certainly help families who have been blighted by a horrible genetic disease, said Robin Lovell-Badge, a professor of genetics and embryology at the Francis Crick Institute in London, who was not involved in the study.

You could quite imagine that in the future the demand would increase. Maybe it will still be small, but for those individuals it will be very important.

The researchers also discovered something unexpected: a previously unknown way that embryos repair themselves.

In other cells in the body, the editing process is carried out by genes that copy a DNA template introduced by scientists. In these embryos, the sperm cells mutant gene ignored that template and instead copied the healthy DNA sequence from the egg cell.

We were so surprised that we just couldnt get this template that we made to be used, said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University and senior author of the study. It was very new and unusual.

The research significantly improves upon previous efforts. In three sets of experiments in China since 2015, researchers seldom managed to get the intended change into embryonic genes.

And some embryos had cells that did not get repaired a phenomenon called mosaicism that could result in the mutation being passed on as well as unplanned mutations that could cause other health problems.

In February, a National Academy of Sciences, Engineering and Medicine committee endorsed modifying embryos, but only to correct mutations that cause a serious disease or condition and when no reasonable alternatives exist.

Sheldon Krimsky, a bioethicist at Tufts University, said the main uncertainty about the new technique was whether reasonable alternatives to gene editing already exist.

As the authors themselves noted, many couples use pre-implantation genetic diagnosis to screen embryos at fertility clinics, allowing only healthy ones to be implanted. For these parents, gene editing could help by repairing mutant embryos so that more disease-free embryos would be available for implantation.

Hank Greely, director of the Center for Law and the Biosciences at Stanford, said creating fewer defective embryos also would reduce the number discarded by fertility clinics, which some people oppose.

The larger issue is so-called germline engineering, which refers to changes made to embryo that are inheritable.

If youre in one camp, its a horror to be avoided, and if youre in the other camp, its desirable, Dr. Greely said. Thats going to continue to be the fight, whether its a feature or a bug.

For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos. (The new study was funded by Oregon Health and Science University, the Institute for Basic Science in South Korea, and several foundations.)

The authors say they hope that once the method is optimized and studied with other mutations, officials in the United States or another country will allow regulated clinical trials.

I think it could be widely used, if its proven safe, said Dr. Paula Amato, a co-author of the study and reproductive endocrinologist at O.H.S.U. Besides creating more healthy embryos for in vitro fertilization, she said, it could be used when screening embryos is not an option or to reduce arduous IVF cycles for women.

Dr. Mitalipov has pushed the scientific envelope before, generating ethical controversy with a so-called three-parent baby procedure that would place the nucleus of the egg of a woman with defective cellular mitochondria into the egg from a healthy woman. The F.D.A. has not approved trials of the method, but Britain may begin one soon.

The new study involves hypertrophic cardiomyopathy, a disease affecting about one in 500 people, which can cause sudden heart failure, often in young athletes.

It is caused by a mutation in a gene called MYBPC3. If one parent has a mutated copy, there is a 50 percent chance of passing the disease to children.

Using sperm from a man with hypertrophic cardiomyopathy and eggs from 12 healthy women, the researchers created fertilized eggs. Injecting CRISPR-Cas9, which works as a genetic scissors, they snipped out the mutated DNA sequence on the male MYBPC3 gene.

They injected a synthetic healthy DNA sequence into the fertilized egg, expecting that the male genome would copy that sequence into the cut portion. That is how this gene-editing process works in other cells in the body, and in mouse embryos, Dr. Mitalipov said.

Instead, the male gene copied the healthy sequence from the female gene. The authors dont know why it happened.

Maybe human sex cells or gametes evolved to repair themselves because they are the only cells that transmit genes to offspring and need special protection, said Juan Carlos Izpisua Belmonte, a co-author and geneticist at the Salk Institute.

Out of 54 embryos, 36 emerged mutation-free, a significant improvement over natural circumstances in which about half would not have the mutation. Another 13 embryos also emerged without the mutation, but not in every cell.

The researchers tried to eliminate the problem by acting at an earlier stage, injecting the egg with the sperm and CRISPR-Cas9 simultaneously, instead of waiting to inject CRISPR-Cas9 into the already fertilized egg.

That resulted in 42 of 58 embryos, 72 percent, with two mutation-free copies of the gene in every cell. They also found no unwanted mutations in the embryos, which were destroyed after about three days.

The method was not perfect. The remaining 16 embryos had unwanted additions or deletions of DNA. Dr. Mitalipov said he believed fine-tuning the process would make at least 90 percent of embryos mutation-free.

And for disease-causing mutations on maternal genes, the same process should occur, with the fathers healthy genetic sequence being copied, he said.

But the technique will not work if both parents have two defective copies. Then, scientists would have to determine how to coax one gene to copy a synthetic DNA sequence, Dr. Mitalipov said.

Otherwise, he said, it should work with many diseases, a variety of different heritable mutations.

R. Alta Charo, a bioethicist at University of Wisconsin at Madison, who led the committee with Dr. Hynes, said the new discovery could also yield more information about causes of infertility and miscarriages.

She doubts a flood of couples will have edited children.

Nobodys going to do this for trivial reasons, Dr. Charo said. Sex is cheaper and its more fun than IVF, so unless youve got a real need, youre not going to use it.

Read the original here:
In Breakthrough, Scientists Edit a Dangerous Mutation From Genes in Human Embryos - New York Times

Shares of Spark Therapeuticssurged nearly 20 percentWednesday after the Philadelphia gene therapy company revealed promisingresults from a study of its potential one-time therapy for hemophilia A.

Preliminary data from a Phase 1/2 dose-escalation clinical trial of SPK-8011showed human proof-of-concept in three participants, the drug maker said.

The encouraging start for hemophilia A reinforces the strength of our gene-therapy platform and positions us well to potentially transform the current treatment approach for this life-altering disease with a onetime intervention, said Katherine A. High, Sparks president and chief scientific officer.

Hemophilia is a genetic disorder caused by missing or defective factor VIII, a clotting protein. About 20,000 Americans live with hemophilia. The way the medical community has addressed the disorder is to ensure that patients have continuous injections of blood-clotting factors. Patients infuse themselves two to three times a week for the rest of their lives.

In the study, three patientsreceived infusions of vector genomes and no serious adverse events were reported, Spark said. One person has been followed for 23 weeks and another for 12 weeks. The initial dose created stable factor VIII levels with no spontaneous bleeds, the company said.

For a third patient, the genome dose was doubled and that persons factor VIII activity level is tracking proportionally higher, consistent with the dose escalation. So far, the drug has been safe and well tolerated, with no reports of serious adverse events, no thrombotic events, no immune responses, and no elevations of liver enzymes, the company said.

The data must be considered preliminary and one must be careful not to overinterpret them, said Cowen & Co. analyst Phil Nadeau in a client update. That being said, we find the results quite encouraging.

Despite a low starting dose, the gene therapy produced stable and clinically meaningful factor levels sufficient to prevent spontaneous bleeds in patients, Nadeau said. Moreover, the safety profile is clean thus far. The results suggest the company may be able to achieve greater factor levels at higher doses. We find SPK-8011s early data encouraging, and think they suggest that Spark has a viable and competitive hemophilia A program.

Spark will present full data at a medical conference in December.

The hemophilia A results, though early, along with previously reported data for the companys hemophilia B candidate, confirm Sparks thought leadership in hemophilia gene therapy, and the likelihood of achieving a leading position in the overall hemophilia market (currently $7 billion, growing to $14 billion in 2030), Chardan Capital Markets analyst Gbola Amusa said in a client note. Chardan raised its peak earnings forecast for Sparks hemophilia A therapy to $1.3 billion, up from $397 million.

Sparks lead drug, a treatment for rare inherited blindness, is under priority review with the U.S. Food and Drug Administration, with a possible approval date of Jan. 12, 2018. If approved, it would be the first gene therapy for a genetic disease in the United States.

Spark, which was spun out of Childrens Hospital of Philadelphia, reported a second-quarter financial loss of $74.4 million in the quarter ended June 30, or $2.40 per share, on revenue of $1.5 million from itscollaboration with Pfizer Inc. for hemophilia B.

Sparks shares have risen 58 percent since Jan. 1 and 37 percent in the last 12 months. The stock closed up 19.72 percent, or $13.13, to $79.72.

Published: August 2, 2017 1:12 PM EDT

We recently asked you to support our journalism. The response, in a word, is heartening. You have encouraged us in our mission to provide quality news and watchdog journalism. Some of you have even followed through with subscriptions, which is especially gratifying. Our role as an independent, fact-based news organization has never been clearer. And our promise to you is that we will always strive to provide indispensable journalism to our community. Subscriptions are available for home delivery of the print edition and for a digital replica viewable on your mobile device or computer. Subscriptions start as low as 25 per day.We're thankful for your support in every way.

Excerpt from:
Philly gene therapy company reports early promising hemophilia A results - Philly.com

Chiesi has cut its ties to uniQures hemophilia B gene therapy. The split gives uniQure full rights to AMT-060 but leaves it without a partner to cofund R&D as it closes in on the start of a pivotal trial.

Italian drugmaker Chiesi picked up the rights to commercialize AMT-060 in certain markets in 2013 as part of a deal that also gave it a piece of Glybera, the gene therapy that made history by coming to market in Europe only to flop commercially. Chiesi backed out of the Glybera agreement earlier this year and has now completed its split from uniQure by terminating the hemophilia B pact.

Amsterdam, the Netherlands-based uniQure framed the termination as it reacquiring the rights to AMT-060, rather than Chiesi dumping the program. But as the deal will see money transfer from Chiesi to uniQure and the former stated a shift in priorities prompted it to sever ties to AMT-060, it seems clear the Italian drugmaker wanted to exit the agreement.

That leaves uniQure facing the prospect of taking AMT-060 into a pivotal trial without the financial support of a partner. Chiesi and uniQure have evenly shared R&D costs since 2013. The loss of the support of Chiesi will add $3 million to uniQures outlay this year, although the Dutch biotech still thinks it has enough cash to take it into 2019.

After a trying time on public markets dotted with stock drops following unfavorable comparisons to Spark Therapeutics rival hemophilia B program, uniQure is less well equipped to raise more money than in the past. But uniQure CEO Matthew Kapusta spun the regaining of full rights to the gene therapy as a boost for the company.

We believe uniQure is better positioned to accelerate the global clinical development plan, maximize shareholder return on our pipeline and take advantage of new potential opportunities related to the program, Kapusta said in a statement.

If the potential opportunities are to include a deal covering AMT-060, uniQure must persuade a potential partner of the merits of its asset. UniQure has sought to focus attention on the durable clinical benefits associated with AMT-060 but investors have fixated on Sparks clear advantage in terms of Factor IX activity.

More:
Chiesi dumps uniQure's hemophilia B gene therapy - FierceBiotech

Man's best mend Gene therapy reverses muscular dystrophy symptoms in dogs Digital Trends Their solution involves using gene therapy to restore muscle strength and stabilize clinical symptoms. This is achieved by way of a shortened version of the dystrophin gene, containing just 4,000 base pairs, which is combined with a viral vector and ... and more »

Read more:
Man's best mend Gene therapy reverses muscular dystrophy symptoms in dogs - Digital Trends

Xconomy Boston

Gene therapy offers the potential for a long-lasting, if not permanent, treatment for an inherited disease, but cells that divide rapidly, such as those in the liver, present a thorny problem. Because of how they insert themselves in the cells, some forms of gene therapy get diluted as the cells divide.

Its a particular problem in growing children. Cambridge, MA-based LogicBio says it has developed a workaround by combining gene editing with gene therapy. The firm has raised $45 million in additional capital to help bring this technology into human testing, and it is moving from California to the LabCentral shared incubator space in Cambridges Kendall Square.

LogicBio calls its technology GeneRide. The company says its approach can transfer genetic material to specific sites to repair a faulty genetic sequence. The companys focus is metabolic disorders that affect the liver in children. Published research shows that metabolic disorders of the liver can progress to injury affecting other organs. In rare cases, the severity of the disease requires a pediatric liver transplant.

If GeneRide works as the company envisions, the gene therapy would offer a one-time treatment that avoids side effects.

London-based Arix Bioscience (LSE: ARIX) led the Series B round of investment, which was joined by new investors OrbiMed, Edmond De Rothschild Investment Partners, Pontifax, and SBI Japan-Israel Innovation Fund. Earlier investor OrbiMed Israel Partners also joined in the latest investment. In total, LogicBio says it has raised approximately $50 million in financing to date.

Gene therapy remains largely experimental. UniQure (NASDAQ: QURE) received the Western worlds first gene therapy approval in 2012 for alipogene tiparovec (Glybera), a treatment for a rare metabolic disorder. But earlier this year, the company, split between the Netherlands and Lexington, MA, announced it would not seek renewal of its conditional approval, set to expire in October. Patient demand for the drug was limited and the company did not expect that to change.

The first U.S. approval could come soon. Philadelphia-based Spark Therapeutics (NASDAQ: ONCE) is awaiting an FDA decision on a gene therapy for an inherited form of blindness. Cambridge-based Bluebird Bio (NASDAQ: BLUE) last week released early data from a Phase 3 study in patients with beta-thalassemia, a rare blood disorder.

The technologies underlying LogicBios approach were developed at Stanford University by company co-founders Mark Kay, Adi Barzel, and Leszek Lisowski. In addition to its Cambridge site, the company also has scientists in Tel Aviv, Israel.

Frank Vinluan is editor of Xconomy Raleigh-Durham, based in Research Triangle Park. You can reach him at fvinluan [at] xconomy.com

Read the original here:
LogicBio Lands $45M for Gene Therapies in Rare Pediatric Diseases - Xconomy

Author's note: The following consists of excerpts from my 45-page May 30 report on bluebird bio (NASDAQ:BLUE), Kite Pharma (NASDAQ:KITE), and Juno Therapeutics (NASDAQ:JUNO). The focus in this submission is BLUE. Please check out my Seeking Alpha profile for important information. Global Gene Therapy Market

The gene therapy market is gaining popularity in the global medical community. The advent of advanced techniques for gene transfer has enabled the use of gene therapy for various new applications. Although it is still at an infant stage, its promise has led to a range of bullish estimates. Market research firm BCC Research forecasts the global market for DNA vaccines to grow at a 54.8% CAGR to $2.7 bln by 2019, while two other observers - Roots Analysis and Research and Markets - predict the gene therapy market as a whole to reach ~$11 bln by 2025. Another report from market intelligence firm Transparency Market Research forecasts that the global stem cell market will grow at a CAGR of > 20% in the next few years and said there is a rich pipeline of more than 500 cell and gene therapy products, which will drive significant capacity as the pipeline matures and progresses to commercial supply.

Key factors driving market growth include demand for novel and efficient therapies to treat cancers and other indications with high unmet needs. Other market drivers include completion of the human genome project, rising incidence and prevalence of cancers and other critical diseases, and the prospective launch of gene therapies in major global markets.

Most gene therapy products are in the pre-clinical or clinical research stage. To-date, there are only five marketed drugs, namely Glybera, Neovasculogen, Gendicine, Rexin-G, and Oncorine. However, these products constitute very little revenue for the gene therapy market. Most revenue for the gene therapy market is generated from products used in clinical trials.

Need for gene therapy: It is estimated that approximately 5% of the global population suffers from a rare disease, and half of the global population affected by rare diseases are children, making rare disease treatment a concern for children across the globe. There are about 7,000 known rare diseases that comprise the most complex healthcare challenges for researchers and health professionals - with most being difficult to diagnose due to heterogeneity in disease epidemiology.

Rare diseases that affect 200,000 people in the US (as per the FDA definition) and a similar percentage in Europe are typically genetic in nature and, thus, present a significant unmet need for potential regimes in the market.

As per World Health Organization, 80% of rare diseases are caused due to genetic abnormality and are inherited for generations. Approximately 5% of the rare diseases have a treatment, and most of the current therapeutic approaches include gene therapy and cell therapy. A significant gap between demand and supply of rare disease drugs is expected to create a massive opportunity for manufacturers and researchers in the area of rare disease treatment.

How Does Gene Therapy Work?

Advances in biotechnology have brought gene therapy to the forefront of medical research. The prelude to successful gene therapy, the efficient transfer and expression of a variety of human gene into target cells, has already been accomplished in several systems.

Gene therapy may be defined as the introduction of genetic material into defective cells for a therapeutic purpose. While gene therapy holds great potential as an effective means for selective targeting and treatment of disease, the field has seen relatively slow progress in the development of effective clinical protocols. Although identifying genetic factors that cause a physiological defect is straightforward, successful targeted correction techniques are proving continually elusive. Hence, safe methods have been devised to do this (using several viral and no-viral vectors). Two main approaches have emerged in-vivo modification and ex-vivo modification. Retrovirus, adenovirus, adeno-associated virus are suitable for gene therapeutic approaches; these are based on permanent expression of the therapeutic gene. Non-viral vectors are far less efficient than viral vectors, but they have advantages due to their low immunogenicity and large capacity for therapeutic DNA.

Viral Vectors: These are virus-based vectors. Examples include retrovirus vector, adeno virus vector system, adeno associated virus vector, and herpes simplex virus. Extensive research is being conducted on the various viral vectors used in gene delivery. Non-viral vectors: Examples of non-viral vector systems include pure DNA constructs, lipoplexes, DNA molecular conjugates, and human artificial chromosomes. Owing to the following advantages, non-viral vectors have gained significant importance in the past few years as they are less immune-toxic, there is risk-free repeat administration and relative ease of large-scale production.

A major disadvantage is that the corrected gene needs to be unloaded into the target cell, and the vector has to be made to reach the required treatment site.

Gene therapy has transitioned from the conceptual, technology-driven, laboratory research, to clinical trial stages for a wide variety of diseases. In addition to curing genetic disorders such as Hemophilia, Chronic Granulomatous Disorder, and Severe Combined Immune Deficiency (ADA-SCID), it is also being tested to cure acquired diseases such as cancer, neurodegenerative diseases, influenza, and hepatitis.

Gene therapy is not limited to any particular disease. It is proving to be a promising treatment for rare diseases such as X-linked adrenoleukodystrophy. The therapy has proved effective in research conducted for the following diseases:

Fat Metabolism Disorder: Gene therapy is used to correct rare genetic diseases caused due to lipoprotein lipase deficiency. This deficiency leads to fat molecules clogging the bloodstream. An adeno-associated virus vector is used to deliver the corrected copy of the LPL to the muscle cells. This corrected copy prevents excess accumulation of fat in the blood by breaking down the fat molecules. In 2012, the EU approved Glybera, the first viral gene therapy treatment for LPLD, manufactured by uniQure (NASDAQ:QURE). Glybera is likely to be approved for the American market by 2018.

Adenosine Deaminase Deficiency: Gene therapy has successfully been used to treat another inherited immune disorder - ADA deficiency. More importantly, none of the patients undergoing this treatment developed any other disorder. The retroviral vector is used in multiple small trials to deliver the functional copy of the ADA gene. Primarily, all the patients involved in these trials did not require any injection of ADA enzyme as their immune functions had immensely improved.

Severe Combined Immune Deficiency: A lot of documented work is already available regarding treating this immunodeficiency with gene therapy; however, clinical trials have not shown promising results. The viral vectors used during the trials triggered leukemia in patients. Since then, focus of the research and trials has been on preparing new vectors that are safe and do not cause cancer.

Hemophilia: Patients with hemophilia suffer excessive blood loss as the blood clotting protein (Factor IX) is absent. Researchers have successfully inserted the missing gene in the liver cells using an adeno-associated viral vector. After undergoing this treatment, patients experienced less bleeding as their body was able to create some of the Factor IX protein.

Cystic Fibrosis (CF): CF is a chronic lung disease caused due to a faulty CFTR gene. Genes are injected into cells using a virus. Recent studies also include testing the cationic liposome (a fatty container) to deliver DNA to the faulty CFTR gene, thus making the use of the non-viral gene carrier more successful. Phase II trials using this therapy were published in early 2015, which promised a novel therapeutic approach to CF.

-thalassemia: Clinical trials on gene therapy for -thalassemia (the faulty beta-globin gene, which codes for an oxygen-carrying protein in RBC) can be tracked back to 2007. Blood stem cells were taken from the patients bone marrow, and a retrovirus was used to transfer a working copy of the faulty gene. The modified stem cells were re-injected into the body to supply functional red blood cells. This treatment, once conducted, lasted over seven years, with the patient not undergoing blood transfusion during this time.

Hereditary Blindness: Currently, gene therapy is being tested to treat degenerative form of inherited blindness, where patients lose light-sensing cells in their eyes over time. Experimental data suggests that the animal models of a mouse, rat, and dog show slow or even reverse vision loss using gene therapy. The most important advantage associated with gene therapy for eye disorders is that AAV (adeno-associated virus) cannot shift from the eye to other body parts and hence does not cause an immune reaction.

Parkinson's Disease: Patients with Parkinson's disease lose the ability to control their movement as their brain cells stop producing the dopamine molecule used for signaling. A small group of patients showed improved muscle control when a small area of their brain was treated with a retroviral vector that contained dopamine-producing genes.

This is because cancer genetics is a novel treatment method, marked by high R&D costs. The therapy targets diseases with high unmet needs; this has been the driving force behind academic research laboratories, small biotech firms, and large pharmaceutical companies. The therapy is of short-duration treatment or mostly one-time treatment customized to individuals and often in small patient populations.

bluebird bio (BLUE) is a clinical-stage biotechnology company that focuses on developing transformative gene therapies for severe genetic diseases and cancer. Its product candidates include Lenti-D, which is in Phase II/III clinical studies for the treatment of cerebral adrenoleukodystrophy - a rare hereditary neurological disorder - and LentiGlobin, which is in four clinical studies for the treatment of transfusion-dependent beta-thalassemia and severe sickle cell disease. The companys lead product candidate is bb2121, a chimeric antigen receptor (CAR) T cell receptor (TCR) product candidate that is in Phase I trial for the treatment of relapsed/refractory multiple myeloma.

The company's gene therapy platform is based on viral vectors that utilize a non-replicating version of the Human Immunodeficiency Virus Type 1 (HIV-1). Its lentiviral vectors are used to introduce a functional copy of a gene to the patient's own isolated hematopoietic stem cells (HSCs) in the case of its LentiGlobin and Lenti-D product candidates, or the patient's own isolated white blood cells, which include T cells, in the case of its bb2121 product candidate.

BLUE has a strategic collaboration with Celgene Corporation (NASDAQ:CELG) to discover, develop, and commercialize disease-altering gene therapies in oncology; with Kite Pharma (KITE) to develop and commercialize second generation T cell receptor product candidates against an antigen related to certain cancers associated with the human papilloma virus; and with Medigene (Germany) for the research and development of (TCR) product candidates directed against approximately four antigens for the treatment of cancer indications. Founded in 1992 and headquartered in Cambridge, Massachusetts, the company was formerly known as Genetix Pharmaceuticals and later changed its name to bluebird bio (Incorporated) in September 2010.

With its lentiviral-based gene therapies, T cell immunotherapy expertise, and gene-editing capabilities, BLUE has built an integrated product platform with broad potential application for severe genetic diseases and cancer. BLUE's approach to gene therapy is based on viral vectors that utilize the Human Immunodeficiency Virus Type 1 or HIV-1. The HIV-1 vector is stripped off all the components that allow it to self-replicate and infect additional cells. HIV-1 is part of the lentivirus family of viruses. The vectors are used to introduce a modified copy of a gene from the patients own blood stem cells called hematopoietic stem cells (HSC), which reside in the patient's bone marrow. HSCs divide cells that allow for sustained expression of the modified gene.

Lenti-D

bluebird is developing the Lenti-D product candidate to treat patients with cerebral adrenoleukodystrophy.

Adrenoleukodystrophy is a rare X-linked, metabolic disorder caused by mutations in the ABCD1 gene, which results in a deficiency in adrenoleukodystrophy protein, or ALDP, and subsequent accumulation of very long-chain fatty acids. Symptoms of CALD usually occur in early childhood and progress rapidly if untreated, leading to severe loss of neurological function and eventual death.

Completed non-interventional retrospective study (the ALD-101 Study)

CALD is a rare disease, and data on the natural history of the disease, as well as the efficacy and safety profile of allogeneic HSCT, is limited in scientific literature. To properly design clinical studies of Lenti-D and interpret the efficacy and safety results thereof, at the recommendation of the FDA, bluebird performed a non-interventional retrospective data collection study to assess the natural course of the disease in CALD patients that were left untreated in comparison with the efficacy and safety data obtained from patients that received allogeneic HSCT.

For this study, data was collected from four US sites and one French site on a total of 137 subjects, 72 of whom were untreated, and 65 were treated with allogeneic HSCT.

Starbeam Study (ALD-102) - Phase II/III clinical study in subjects with CALD

The company is currently conducting a Phase II/III clinical study of Lenti-D product candidate in the US, referred to as the Starbeam Study (ALD-102), to examine the safety and efficacy of Lenti-D product candidate in subjects with CALD. The study was fully enrolled in May 2015; however, in December 2016, the company amended the protocol for this study to enroll up to an additional eight subjects in an effort to enable the first manufacture of Lenti-D product candidate in Europe and the subsequent treatment of subjects in Europe, and to bolster the overall clinical data package for potential future regulatory filings in the US and Europe. It intended to begin treating the additional patients in early 2017.

The ALD-103 (observational) study

bluebird is also conducting the ALD-103 study, an observational study of subjects with CALD treated by allogeneic HSCT. This study is ongoing and is designed to collect efficacy and safety outcomes data in subjects who have undergone allogeneic HSCT over a period that is contemporary with the Starbeam study.

Lentiglobin Product

Transfusion-dependent -thalassemia (TDT)

-thalassemia is a rare hereditary blood disorder caused by a mutation in the -globin gene, resulting in the production of defective red blood cells, or RBCs. Genetic mutations cause the absence or reduced production of beta chains of hemoglobin, or -globin, preventing the proper formation of hemoglobin A, which normally accounts for more than 95% of the hemoglobin in the blood of adults.

Limitations of current treatment options

In geographies where treatment is available, patients with TDT receive chronic blood transfusion regimens. These regimens consist of regular infusions with units of packed RBC, or pRBC, usually every three to five weeks, to maintain hemoglobin levels and control symptoms of the disease.

The only potentially curative therapy for -thalassemia today is allogeneic HSCT. However, complications of allogeneic HSCT include risk of engraftment failure in unrelated human-leukocyte-antigen, or HLA, matched patients, risk of life-threatening infection, and risk of GVHD - a common complication in which donor immune cells (white blood cells in the graft) recognize the cells of the recipient (the host) as foreign and attack them. As a result of these challenges, allogeneic HSCT can lead to significantly high mortality rates, particularly in patients treated with cells from a donor who is not a matched sibling and in older patients. Overall, TDT remains a devastating disease with an unmet medical need.

The Northstar Study (HGB-204) Phase I/II clinical study in subjects with TDT

The Northstar study is a single-dose, open-label, non-randomized, multi-site Phase I/II clinical study in the US, Australia, and Thailand to evaluate the safety and efficacy of the LentiGlobin product candidate in increasing hemoglobin production and eliminating or reducing transfusion dependence following treatment. In March 2014, the first subject with TDT was treated in this study, and, in May 2016, the study was fully enrolled.

The study enrolled 18 adults and adolescents. To be eligible for enrollment, subjects had to be between 12 and 35 years of age, with a diagnosis of TDT, and received at least 100 mL/kg/year of pRBCs or more than or equal to eight transfusions of pRBCs per year in each of the two years preceding enrollment.

Efficacy will be evaluated primarily by the production of 2.0 g/dL of hemoglobin A containing A-T87Q-globin for the six-month period between 18 and 24 months, post transplants. Exploratory efficacy endpoints include RBC transfusion requirements (measured in milliliters per kilogram) per month and per year, post transplants.

The HGB-205 study Phase I/II clinical study in subjects with TDT or with severe SCD

bluebird is conducting the HGB-205 study, a Phase I/II clinical study, in France to study the safety and efficacy of its LentiGlobin product candidate in the treatment of subjects with TDT and of subjects with severe SCD. In December 2013, the company said that the first subject with TDT had been treated in this study; in October 2014, bluebird declared that the first subject with severe SCD had been treated in this study. By February 2017, the study had been fully enrolled.

bluebird is conducting HGB-206 multi-site Phase I clinical study in the US to evaluate the safety and efficacy of its LentiGlobin product candidate for the treatment of subjects with severe SCD. In October 2016, the company amended the protocol of its HGB-206 study to expand enrollment and incorporate several process changes, including updated drug product manufacturing process. Enrollment had begun under this amended protocol, and in February 2017, the company treated the first subject under this amended protocol.

The Northstar-2 Study (HGB-207) Phase III study in subjects with TDT and a non-0/0 genotype

The Northstar-2 study is an ongoing single-dose, open-label, non-randomized, international, multi-site Phase III clinical study to evaluate the safety and efficacy of the LentiGlobin product candidate to treat subjects with TDT and non-0/0 genotype. Approximately 23 subjects will be enrolled in the study, consisting of at least 15 adolescent and adult subjects between 12 and 50 years of age at enrollment and at least eight pediatric subjects less than 12 years of age at enrollment. In December 2016, the first subject had received treatment with the LentiGlobin product candidate.

The planned Northstar-3 Study (HGB-212) Phase III Study for TDT in subjects with TDT and a 0/ 0 genotype

The company plans the initiation of HGB-212, a Phase III clinical study of LentiGlobin in patients with TDT and the 0/0 genotype in 2H FY2017.

bluebird expects to enroll up to 15 adult, adolescent, and pediatric subjects. The company anticipates that the primary endpoint of the Northstar-3 study will be transfusion reduction, which is defined as a demonstration of a reduction in the volume of pRBC transfusion requirements in the post-treatment time period of 12-24 months, compared with the average annual transfusion requirement in the 24 months prior to enrollment.

Sickle Cell Disease

SCD is an inherited disease that is caused by a mutation in the -globin gene; this results in sickle-shaped red blood cells. The disease is characterized by anemia, vaso-occlusive crisis, infections, stroke, overall poor quality of life, and, sometimes, early death. Where adequate medical care is available, common treatments for patients with SCD largely revolves around the management and prevention of acute sickling episodes. Chronic management may include hydroxyurea and, in certain cases, chronic transfusions. Given the limitations of these treatments, there is no effective long-term treatment. The only advanced therapy for SCD is allogeneic hematopoietic stem cell transplantation (HSCT). Complications of allogeneic HSCT include a significant risk of treatment-related mortality, graft failure, graft-versus-host disease, and opportunistic infections - particularly in patients who undergo non-sibling-matched allogeneic HSCT.

In March 2017, bluebird announced the Publication of the Case Study on the First Patient with Severe Sickle Cell Disease Treated with Gene Therapy in The New England Journal of Medicine. Patient 1204, a male patient with S/S genotype, was enrolled in May 2014 at 13 years of age into the HGB-205 clinical study. The patient underwent a regular transfusion regimen for four years prior to this study. Over 15 months since transplant, no SCD-related clinical events or hospitalizations occurred - contrasting favorably with the period before the patient began regular transfusions. All medications were discontinued, including pain medication.

The successful outcome in Patient 1204 demonstrates the promise of treatment with LentiGlobin gene therapy in patients with severe SCD and serves as a guide to optimize outcomes in future patients.

Celgene Collaboration

In March 2013, BLUE entered into a strategic collaboration with Celgene to advance gene therapy in oncology (cancer), which was amended and restated in June 2015, and amended again in February 2016. The multi-year research and development collaboration focused on applying BLUEs expertise in gene therapy technology to CAR T cell-based therapies, to target and destroy cancer cells. The collaboration now focuses exclusively on anti- B-cell maturation antigen BCMA product candidates for a new three-year term.

Under the terms of the Amended Collaboration Agreement, for up to two product candidates selected for development under the collaboration, BLUE is responsible for conducting and funding all research and development activities performed up through completion of the initial Phase I clinical study of such a product candidate.

In February 2016, Celgene exercised its option to obtain an exclusive worldwide license to develop and commercialize bb2121, the first product candidate under the Amended Collaboration Agreement, and paid the associated ($10 million) option fee. BLUE will share equally in all costs related to developing, commercializing, and manufacturing the product candidate within the US, if it elects to co-develop and co-promote bb2121 with Celgene. In case BLUE does not exercise its option to co-develop and co-promote bb2121, it will receive an additional fee (of $10 million).

Summary

All three names in my May 30, 2017, (45-page) report are from the same space, and I highly recommend taking a look at the entire report before making an investment decision. It is available on request.

This industry is in its infancy - most trials are only in Phase I or Phase II. The companies do not have earnings yet, and that makes them difficult to value today. In my opinion, the upside here is significant, but you may have to hold on to these names for a few years in order to realize that upside, because today an argument can be made that the stocks have gotten a little bit ahead of themselves.

I am keeping my Buy recommendation on Juno (unchanged), and I am keeping my Hold recommendation on Kite (unchanged). There are currently seven institutions (each) with stakes of at least 250 million dollars in BLUE. There are nine institutions (each) with stakes of at least 175 million dollars in KITE. With JUNO, the institutional ownership is much lower - many institutions probably got shaken out following deaths on the Juno trials last year. In my opinion, the market over-reacted to those deaths. In fact, the shares have already bounced significantly since the low from last year following that market over-reaction (and insiders bought $500,000 worth of Juno shares recently).

I went in and out of KITE twice in the last couple of years and locked in gains of 35% both times. I most recently exited KITE at $87 a share on March 13.

The 52-week high on BLUE is $124, and the all-time high is $194.

There are 8,000,000 shares short, and that is more than 10X the average daily volume.

My recommendation is to allocate 3% portfolio weight to this industry: 1.5% to BLUE, 0.75% to KITE, and 0.75% to JUNO.

I remember an analyst (many years ago) on CNBC defending his Sell recommendation on Amazon (NASDAQ:AMZN). It was trading at $100/share at the time. He defended the Sell rating by saying it loses money on every book it sells. AMZN recently hit $1,000 today. The lesson here is do not be afraid to invest in names with multi-billion market caps that are without EPS today. With KITE, BLUE, and JUNO, you must look out 3-5 years.

Sources

Why bluebird bio Stock Surged 20.7% Higher in January

Risks - Mayo Clinic

bluebird bio Reports First Quarter 2017 Financial Results and Recent Operational Progress

bluebird bio Announces Publication of Case Study on First Patient with Severe Sickle Cell Disease Treated with Gene Therapy in The New England Journal of Medicine

Annual Report 10-K

Quarterly Report 10-Q

Press Release | Investor Relations | Bluebird Bio

Kite Pharma Posts Q1 Loss, Reveals CAR-T Patient Death

SHAREHOLDER ALERT: Bronstein, Gewirtz & Grossman, LLC Announces Investigation of Kite Pharma, Inc. (KITE)

KITE INVESTOR ALERT: Faruqi & Faruqi, LLP Encourages Investors Who Suffered Losses Exceeding $100,000 Investing In Kite Pharma, Inc. To Contact The Firm

SHAREHOLDER ALERT: Levi & Korsinsky, LLP Announces the Commencement of an Investigation Involving Possible Securities Fraud Violations by the Board of Directors of Kite Pharma, Inc.

Kite Investors See An Uncomfortable Parallel With Juno

Kite Pharma: History In The Making?

Kite Pharma: Still Time To Get In Ahead Of Lead Oncology Treatment Approval

Here's What's Dragging Kite Pharma Inc. Down Today -- The Motley Fool

Global Gene Therapy Market to Reach US$316 Million by 2015, According to a New Report by Global Industry Analysts, Inc.

Gene Therapy Market information, Current Trends Analysis, Major Players and Forecast 2024

Gene Therapies Market will generate $204m in 2020

Cancer Gene Therapy Market size to exceed $4.3bn by 2024

Could gene therapy become biotech's growth driver in 2017?

Cell Therapy 2016 - Year in Review (part 1)

Cancer Gene Therapy Market Size, Share, Industry Report 2024

Gene Therapy Market information, Current Trends Analysis, Major Players and Forecast 2024

Gene Therapy Clinical Trials Worldwide

Human Gene Therapy (PDF)

Aranca Report - GENE THERAPY: Advanced Treatments for a New Era

International Journal Of Pharma Sciences and Research (IJPSR) - Gene therapy: Current status and future perspectives Gene Therapy Institute for Clinical and Economic Review

See more here:
Biotech Gene Therapy Names Juno, Kite, And bluebird bio Still Have Room To Run - Seeking Alpha

Inherent Complexity

The inherent complexity of viral vector-based products, due to their physical size, formulation, and the fact that they often utilize a combined drug targeting/delivery vehicle function, makes their physical and biological characterization highly challenging from a regulatory perspective. Consequently, a fallback approach is adopted where the product is defined by the manufacturing process. This approach then makes the introduction of potentially product-impacting process changes difficult to implement and by default, the process becomes locked down within the early stages of development, severely restricting the scope for process improvement and scale up.

Classical process scale up tends to be via a vertical approach, with a focus on increasing the size of single operations (such as fermentation vessels) while keeping similar labor levels, subsequently achieving reduction in cost. This approach is valid if the process is well understood and amenable to linear scale up. The reality is that a large number of the key operations in the production of viral vectors are neither well characterized nor easily scaled. Lack of time and analytical tools will eventually direct developers to take a more horizontal approach to process scale up.

It seems likely that scale up will be based on limited vertical scale up, with multiple and overlapping production streams, potentially exploiting options around the adoption of closed single-use production systems to maximize outputs from production facilities. While this may not be the most efficient approach with regard to labor and facility costs and end-product testing, it is likely to be the only realistic option for many product development groups.

It is inevitable that some process changes will need to be introduced, for example, the requirement to replace purification of vectors by ultracentrifugation, as these processes are perceived as not only being unscalable, but also as highly operator-dependent with regard to yield and purity. The challenge becomes how engineers replace this type of operation. From a regulatory perspective, the key is an understanding of the critical quality attributes (CQAs) that impact product safety, purity, and potency; the critical process parameters (CPPs) required to control them; and the availability of the tools to measure CPPs.

This approach then, in theory, will allow process development groups to develop strategies for introducing and verifying the impact of desired process changes. However, the successful process development of these legacy processes will be dependent on the availability of suitable in-process and final-product assays. There is a clear regulatory, as well as operational, need for drug developers to invest in the analytical tools required to achieve greater understanding of AAV vectors and the processes used to make them for the products to receive commercial licensing.

The production of vectors through transient production routes entails a complex materials supply chain. At the front end is the supply of plasmid DNA constructs used to generate the vectors; clearly the quantities required will not only increase proportionally with the increased scale of vector manufacturing, but also, the associated quality requirements will be increased, moving from materials made to traceable standards to those made to GMP-grade standards (Figure 2). For early-phase development, non-GMP-grade plasmids may be used for the production of material for proof-of principle clinical studies. However, this may not be the case for commercial vectors, where GMP-grade plasmids may be required. One consequence of this will be the potential need for manufacturers to align with suppliers that have large-scale GMP capabilities to ensure the timely and secure delivery of plasmid supplies to support late clinical and commercial production.

At the end of the supply chain is the production of the viral vector drug product. For early-stage development, relatively little focus is given to either the product formulation or the filling process. There is often good reason for this, as material for such development studies is in very short supply, with all available material often directed into clinical studies to demonstrate product efficacy.

The result of this is that the basic formulations used in early-stage development are carried forward into late-stage trials, with the products 0.2-m filtered and hand filled into glass vials and stored at 80C.

Future development activities in the AAV field will need to be focused on identifying formulations that provide long-term stability, potentially moving to +28C storage, and generating meaningful stability data. Fully defining the drug product manufacturing process will also ensure the retention of product titers and activity throughout the manufacturing process, including activities such as inspection and labeling.

In conclusion, we are in exciting times with a number of these potentially life-changing products coming through to clinic. However, if we are to bring these products efficiently to the market, developers will need to adopt pragmatic and informed solutions for the manufacturing challenges that lie ahead.

Go here to read the rest:
Manufacturing of AAV Vectors for Gene Therapy - Genetic Engineering & Biotechnology News

An 11-year-old girl in Massachusetts is at the forefront of a disease so rare, that it is believed only 22 people worldwide have been diagnosed with it. Talia Duff, who was born with Down syndrome and later diagnosed with Charcot-Marie-Tooth Neuropathy Type 4J (CMT4J), is slated to be among the first to enroll in a clinical trial that is awaiting FDA approval after her parents refused to watch her fall victim to the degenerative genetic disease.

Its a horrible feeling to go to a doctor and be told that theres nothing that can be done that the best you can do is try to make your child comfortable and enjoy the time you have together, John Duff, Talias dad, told PEOPLE. I learned to cherish moments in life that I would otherwise take for granted.

PREGNANT MOM DELAYS CANCER TREATMENT TO PROTECT UNBORN TWINS

The Duff family, which includes mom Jocelyn and older sister Teaghan, had noticed Talia struggling to crawl at around age four, and a regression in a number of other motor skills that at the time was attributed to her Down syndrome, and later to Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP). Subsequent failed therapies and a diagnoses of osteoporosis due to prescribed steroids caused her parents to push for another diagnosis at Boston Childrens Hospital, according to a post on the familys Cure CMT4J Foundation website.

We learned that Talia did not in fact have CIDP but instead had an extremely rare form of Charcot Marie Tooth Disease a degenerative, genetic disease called CMT4J, the post read.

MEREDITH VIEIRA SPEAKS OUT ON 'SILENT' BONE DISEASE

The family learned the disease would slowly take over Talias body like a form of amyotrophic lateral sclerosis (ALS), eventually causing paralysis and robbing her of her ability to breathe. In the two years since her diagnosis, Talia lost her ability walk or even raise her arms.

We were supposed to sit back and watch our child live her life in reverse, the post on Cure CMT4J Foundation read. I decided not to accept this. I stayed up late nights pouring over scientific papers and booked appointments with the top CMT doctors in the world. We traveled to the University of Iowa and then Vanderbilt University, where we met Dr. Jun Li.

CHRISTIAN ROCKER RAISING FUNDS FOR BANDMATE WHOSE WIFE DIED HOURS AFTER CHILDBIRTH

It was at the meeting with Li that the Duffs learned of a genetic therapy that could potentially cure Talias disease, but that it was eight-to-ten years away from production. Knowing that time was of the essence for Talia, Jocelyn began connecting with other parent advocates and the family started the Cure CMT4J Foundation with a goal of raising $1 million for research. She met with a team of eight researchers in Maryland, who concluded that the gene therapy would have a lasting effect on Talia, and they are now working to attain proof of concept approval from the FDA, PEOPLE reported.

With approval expected to come later this summer, Jocelyn is prepared to then push for approval of a human clinical trial, with Talia expected to be among the first to receive the gene therapy intravenously.

We feel hope now, Jocelyn told PEOPLE. People have said to me, This is a lot of work for you, and my response is, Hey, you would do this for your child, too. I simply cant stand by and do nothing.

More:
Massachusetts girl may be among first-ever to receive gene therapy for rare disease after parents push for cure - Fox News