Genetics of inherited thrombocytopenias
First Gene Therapy For Tay-Sachs Disease Successfully Given To Two ...
By Miguel Sena-Esteves, UMass Chan Medical School Worcester (US), Feb 15 (The Conversation) Two babies have received the first-ever gene therapy for Tay-Sachs disease after over 14 years of development.Tay-Sachs is a severe neurological disease caused by a deficiency in an enzyme called HexA. This enzyme breaks down a fatlike substance that normally exists in very small, harmless amounts in the brain. Without HexA, however, this fatlike substance can accumulate to toxic levels that damage and kill neurons.
One of the symptoms of this disease was first described in 1883 by British ophthalmologist Warren Tay, who saw a cherry-red spot on the back of the eye of affected infants. In 1887, American neurologist Bernard Sachs described the profound neurological symptoms of Tay-Sachs in a seminal paper:
"... Nothing abnormal was noticed until the age of two to three months, when the parents observed that the child was much more listless than children of that age. ... The child would ordinarily lay upon its back, and was never able to change its position ... It never attempted any voluntary movement ... The child grew steadily weaker, it ceased to take its food properly, its bronchial troubles increased, and finally, pneumonia set in, it died August, 1886."This dismal description of Tay-Sachs remains current, and those with the disease usually die by age 5. Some people develop Tay-Sachs later in life, with symptoms starting in their teens that get progressively worse over many decades.
Unfortunately there is still no treatment for Tay-Sachs. Aggressive medical treatment can extend survival but doesn't improve neurological function. The only effective way to treat Tay-Sachs is to restore the HexA enzyme in the brain. This is difficult, however, because the blood-brain barrier prevents most molecules from passing into the brain.I am a member of a team of researchers from UMass Chan Medical School and Auburn University who developed a gene therapy that may help get around this barrier.
Our treatment uses two harmless viral vectors to deliver DNA instructions to brain cells that teach them how to produce the missing enzyme. Similar techniques have been used to treat a number of related diseases and other conditions.
In the case of Tay-Sachs, these DNA instructions enter the nucleus of these cells and stay there, allowing for long-term production of HexA. Based on our previous studies successfully testing our gene therapy on different animal species, we believe that delivering the treatment to a central part of the brain allows the enzyme to travel along its connections to other regions and to be distributed throughout the entire brain.The first child who received our gene therapy treatment was age 2 ½, with late-stage disease symptoms. Three months after treatment, they had better muscle control and could focus their eyes. Now at age 5, the child is in stable health and is seizure-free, which usually isn't possible for patients at this age. A second child treated at age 7 months had improved brain development by the three-month follow-up and remains seizure-free at a little over age 2.
More testing is needed to confirm whether our treatment can fully stop disease progression. Given that this was the first time our treatment was given to humans, we used a conservative dose below the maximum therapeutic effects we saw in our animal studies. My colleagues and I are currently conducting a follow-up clinical trial to test the safety and efficacy of increasing doses in a larger number of patients.
The increasing cost of manufacturing these treatments makes it extremely difficult, if not impossible, to develop and test gene therapy for many ultrarare diseases where the number of patients worldwide is very small and profitability low.
We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant. This grassroots approach is a common theme in ultrarare disease research - development and testing are often supported by parents, foundations and federal grants.
Our Translational Institute for Molecular Therapeutics programme at UMass Chan Medical School focuses on developing more viral vector gene therapies for an ever-expanding number of ultrarare diseases in collaboration with families and foundations. We believe every patient afflicted with any of the approximately 7,000 rare diseases worldwide deserves a chance at a normal life. (The Conversation) AMS AMS
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Tay Sachs Disease Pipeline Insight Analysis Report: Recent Advancements ...
This is a paid press release. Contact the press release distributor directly with any inquiries.
Company LogoDublin, March 17, 2025 (GLOBE NEWSWIRE) -- The "Tay Sachs Disease Pipeline Insight Analysis Report" drug pipelines has been added to ResearchAndMarkets.Com's offering.
The Tay-Sachs treatment pipeline analysis provides an overview of recent advancements and ongoing clinical trials. The report highlights progress in developing novel therapies, including enzyme replacement therapies, substrate reduction therapies, and gene therapies, aiming for effective disease control and long-term management. It covers innovative approaches such as personalized medicine, which tailors treatments based on individual patient profiles, and advanced diagnostic technologies for improved treatment efficacy.
Tay Sachs Drug Pipeline Outlook
Tay-Sachs disease is a fatal genetic disorder resulting from a deficiency in the enzyme hexosaminidase A. This deficiency leads to the accumulation of GM2 ganglioside in neurons, causing progressive neurological damage. Symptoms include developmental delays, muscle weakness, vision and hearing loss, and severe neurological impairment. Recent advancements focus on enzyme replacement and gene therapies to address the underlying genetic cause and improve patient outcomes.
Recent advancements focus on targeted therapies and personalized medicine to improve patient outcomes by addressing the specific molecular and genetic characteristics of the disease.
In 2023, significant advancements in T-cell lymphoma treatment have been made. The FDA approved IntraBio's Investigational New Drug (IND) application for their lead compound, IB1001. This approval allows IntraBio to commence clinical trials for Tay-Sachs and Sandhoff diseases in the United States and Europe. IB1001, an oral acetylleucine powder, is designed to treat these lysosomal storage disorders by potentially restoring the deficient enzyme activities that cause these conditions.
Key Takeaways
Key players in the Tay-Sachs drug pipeline market include Genzyme, a Sanofi Company, and Aldagen among others. These companies are at the forefront of developing cutting-edge therapies to improve patient outcomes.
The drug pipeline for Tay-Sachs includes promising candidates such as venglustat (GZ402671) and IB1001. These treatments focus on reducing the accumulation of GM2 ganglioside, enhancing lysosomal function, and providing innovative approaches to manage symptoms and improve survival rates.
Regulatory agencies are encouraging the development of novel Tay-Sachs treatments by providing incentives such as fast-track designations and priority reviews. This support is crucial for facilitating quicker access to new and effective therapies for patients, addressing the urgent need for better treatment options in this challenging condition.
Story Continues
Tay Sachs - Pipeline Drug Profiles
Venglustat (GZ402671): Venglustat is an investigational substrate reduction therapy aimed at reducing the accumulation of GM2 ganglioside. Developed by Genzyme, it targets the underlying cause of Tay-Sachs by inhibiting glucosylceramide synthase.
IB1001: IB1001 is a gene therapy candidate designed to deliver a functional HEXA gene to patients, thereby restoring hexosaminidase A enzyme activity and preventing GM2 ganglioside buildup.
Companies Featured
Terence Flotte
Genzyme, a Sanofi Company
IntraBio Inc.
Azafaros A.G.
Natera, Inc.
Exsar Corporation
Azafaros A.G.
Idorsia Pharmaceuticals Ltd.
Talaris Therapeutics Inc.
Aldagen
For more information about this drug pipelines report visit https://www.Researchandmarkets.Com/r/cbrnlx
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First Gene Therapy For Tay-Sachs Disease Successfully Given To Two Children
Two babies have received the first-ever gene therapy for Tay-Sachs disease after over 14 years of development.
Tay-Sachs is a severe neurological disease caused by a deficiency in an enzyme called HexA. This enzyme breaks down a fatlike substance that normally exists in very small, harmless amounts in the brain. Without HexA, however, this fatlike substance can accumulate to toxic levels that damage and kill neurons.
One of the symptoms of this disease was first described in 1883 by British ophthalmologist Warren Tay, who saw a cherry-red spot on the back of the eye of affected infants. In 1887, American neurologist Bernard Sachs described the profound neurological symptoms of Tay-Sachs in a seminal paper:
"… Nothing abnormal was noticed until the age of two to three months, when the parents observed that the child was much more listless than children of that age. … The child would ordinarily lay upon its back, and was never able to change its position … it never attempted any voluntary movement … the child grew steadily weaker, it ceased to take its food properly, its bronchial troubles increased, and finally, pneumonia set in, it died August, 1886."
This dismal description of Tay-Sachs remains current, and those with the disease usually die by age five. Some people develop Tay-Sachs later in life, with symptoms starting in their teens that get progressively worse over many decades.
I am a member of a team of researchers from UMass Chan Medical School and Auburn University who developed a gene therapy that may help get around this barrier. Our treatment uses two harmless viral vectors to deliver DNA instructions to brain cells that teach them how to produce the missing enzyme. Similar techniques have been used to treat a number of related diseases and other conditions.
Unfortunately there is still no treatment for Tay-Sachs. Aggressive medical treatment can extend survival but doesn't improve neurological function. The only effective way to treat Tay-Sachs is to restore the HexA enzyme in the brain. This is difficult, however, because the blood-brain barrier prevents most molecules from passing into the brain.
In the case of Tay-Sachs, these DNA instructions enter the nucleus of these cells and stay there, allowing for long-term production of HexA. Based on our previous studies successfully testing our gene therapy on different animal species, we believe that delivering the treatment to a central part of the brain allows the enzyme to travel along its connections to other regions and to be distributed throughout the entire brain.
The first child who received our gene therapy treatment was age two and a half, with late-stage disease symptoms. Three months after treatment, they had better muscle control and could focus their eyes. Now at age five, the child is in stable health and is seizure-free, which usually isn't possible for patients at this age. A second child treated at age seven months had improved brain development by the three-month follow-up and remains seizure-free at a little over age two.
More testing is needed to confirm whether our treatment can fully stop disease progression. Given that this was the first time our treatment was given to humans, we used a conservative dose below the maximum therapeutic effects we saw in our animal studies. My colleagues and I are currently conducting a follow-up clinical trial to test the safety and efficacy of increasing doses in a larger number of patients.
The increasing cost of manufacturing these treatments makes it extremely difficult, if not impossible, to develop and test gene therapy for many ultrarare diseases where the number of patients worldwide is very small and profitability low.
We were able to deliver these treatments to the children in our ongoing clinical trials thanks only to funding from a generous family whose own child is a participant. This grassroots approach is a common theme in ultrarare disease research; development and testing are often supported by parents, foundations and federal grants.
Our Translational Institute for Molecular Therapeutics program at UMass Chan Medical School focuses on developing more viral vector gene therapies for an ever-expanding number of ultra-rare diseases in collaboration with families and foundations. We believe every patient afflicted with any of the approximately 7,000 rare diseases worldwide deserves a chance at a normal life.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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