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December 18, 2021/MedClub News/--On December 16, 2021, gene therapy company uniQure announced its ongoing Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease, recruiting Preliminary observations of the first four patients in the low-dose cohort
.
In this randomized, blinded clinical trial, 2 of the 4 enrolled patients received AMT-130 and 2 received sham surgery
.
Dr.
Ricardo Dolmetsch, President of UniQure R&D, said: “We are pleased that these data demonstrate the tolerance of AMT-130, which is a potential one-time gene therapy for Huntington’s disease
.
Neurofilament light chain (NfL) is the brain The key biomarkers of injury showed a downward trend in treated patients and returned to baseline levels.
Structural MRI data is consistent with the safety of AMT-130
.
We look forward to evaluating the safety of more patients in ongoing studies.
Biomarkers and functional data
.
"Huntington's disease (HD) is a rare genetic neurodegenerative disease that can cause motor symptoms, behavioral abnormalities, and cognitive decline, including chorea
.
The disease is an autosomal dominant genetic disease, in the first exon of the Huntington gene, there is a repeated amplification of the pathogenic CAG trinucleotide, which leads to the production and aggregation of abnormal proteins in the brain
.
Although the cause of Huntington’s disease is clear, there is currently no approved treatment to delay the onset or slow the progression of the disease
.
▲ Huntington's disease (picture source: trypanophobia.
wordpress) AMT-130 is uniQure's first clinical project focused on the central nervous system (CNS), combined with its proprietary miQURE® platform
.
UniQure’s gene therapy product candidate drug AMT-130 utilizes its proprietary miQURE™ silencing technology and consists of an AAV5 vector carrying artificial micro-RNA (micro-RNA, miRNA).
The production of mutant protein (mHTT)
.
The company believes that the use of AAV vectors to deliver miRNAs directly to the brain to knock down the huntingtin gene non-selectively represents a highly innovative and promising method for the treatment of Huntington's disease
.
The Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease is exploring signals of safety, tolerability, and effectiveness.
It is planned to divide 26 patients with early-stage Huntington’s disease into 10 low-dose cohorts and 16 high-dose cohorts.
Cohort; patients were randomly treated with AMT-130 or sham surgery
.
This multicenter trial includes a 12-month blinded core study period and a 5-year unblinded long-term follow-up
.
Clinical progression of the first batch of patients The first four patients are a heterogeneous group, showing 41-44 CAG repeats of stage I-II early dominant disease, baseline total functional ability score of 10-13 points, total exercise score It is 7-23 points
.
AMT-130 is generally well tolerated in patients treated with lower doses (6x1012 vector genome (vg))
.
So far, no serious adverse events (SAEs) related to AMT-130 have occurred in these patients
.
Two patients receiving treatment after AMT-130 surgery, NfL immediately increased as expected and returned to baseline levels
.
In the two untreated control patients, NfL remained relatively stable
.
During the one-year follow-up, structural magnetic resonance imaging did not show any clinically significant safety findings
.
The measured values of total HTT protein and mutant HTT protein in the cerebrospinal fluid of four patients varied greatly and were inconclusive
.
To date, the safety of AMT-130 in the low-dose cohort supports continued enrollment of patients in the 6x1013vg high-dose cohort
.
So far, 19 patients have participated in the clinical trial, including 9 patients in the 16 high-dose cohort
.
The safety data update for the 10 low-dose cohort patients is expected to be announced after the patients are unblinded in the second quarter of 2022
.
After all patients in the high-dose cohort complete a one-year follow-up, it is expected that complete safety and efficacy data will be obtained from the first two cohorts of phase I/II clinical trials in the first half of 2023
.
Gene therapy strategies for rare diseases At present, there are more than 7,000 rare diseases known worldwide, accounting for about 10% of human diseases
.
Among the various rare diseases, about 80% are caused by genetic defects and are hereditary
.
The World Health Organization (WHO) defines a rare disease as a disease whose number of patients accounts for 0.
65‰ to 1‰ of the total population
.
However, due to the huge population base in our country, the number of patients with rare diseases is not uncommon
.
In recent years, gene therapy technology has made significant progress in the research of hereditary rare diseases, providing a possibility for a complete cure of the disease
.
➤In October 2021, 4D Molecular Therapeutics (4DMT), a gene drug development company based on AAV directed evolution and precise targeting technology, announced that its research gene therapy 4D-310 is 1/ Positive interim results were obtained in phase 2 clinical trials
.
This is the first clinical trial to show that a single-dose gene therapy can increase the AGA enzyme activity in Fabry disease patients to near or higher than normal levels
.
Recommended reading: Targeted AAV vector releases more potential for gene therapy! Data on the treatment of rare diseases is positive Yimai Meng broke the news ➤ In September 2021, PTC Therapeutics announced the latest five-year analysis results of its one-time gene therapy PTC-AADC.
The results showed that they suffer from aromatic L-amino acid decarboxylase deficiency (AADC) ) After receiving PTC-AADC, the children have largely recovered their motor function and cognitive skills, and these improvements are continuous
.
Recommended reading: 5 years of comprehensive improvement! Positive clinical data on gene therapy for children’s rare diseases Yimai Meng broke the news ➤In September 2021, Taysha Gene Therapies announced that its AAV9-based gene replacement therapy TSHA-102 has been awarded the title of orphan drug by the European Commission for the treatment of Rett syndrome
.
Recommended reading: For the treatment of rare diseases! An AAV9 gene therapy has just been designated as an orphan drug by the European UnionYi Mai Meng broke the news ➤ In July 2021, Abeona Therapeutics announced that its new gene therapy ABO-102 is used in the treatment of type A Sanfilippo syndrome (MPS IIIA, also known as mucopolysaccharide).
In the Phase 1/2 clinical trial Transpher A in pediatric patients with dysplasia type IIIA, positive results were obtained
.
Magnetic resonance imaging (MRI) data showed that at the 24th month, compared with untreated patients, ABO-102 had a clinically significant increase in the brain gray matter, corpus callosum, and amygdala in three patients
.
Recommended reading: Treating rare diseases! AAV gene therapy has clinical significance to increase the brain volume of children with medical science.
In May 2021, Orchard Therapeutics announced the gene therapy OTL-101 to treat patients with severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA- SCID) Phase 1/2 clinical trial data
.
The results showed that the overall survival rate of ADA-SCID after receiving gene therapy for 2 and 3 years was 100%
.
Recommended reading: Treating rare diseases in children! Gene therapy shows a survival rate of 100% for fatal diseasesYi Mai Meng revealed that with the advancement of science and technology, the understanding of rare diseases is deepened, the strong support of regulatory policies, and the high attention of research and development companies, rare diseases worldwide The treatment landscape has undergone tremendous changes
.
We look forward to the emergence of more innovative therapies in the future, bringing new hope to patients with rare diseases
.
Reference materials: 1.
https:// -gene-therapy-for-the-treatment-of-huntington-s-disease/2.
http:// Recent articles recommend recent popular conference live broadcast · altaltalt
.
In this randomized, blinded clinical trial, 2 of the 4 enrolled patients received AMT-130 and 2 received sham surgery
.
Dr.
Ricardo Dolmetsch, President of UniQure R&D, said: “We are pleased that these data demonstrate the tolerance of AMT-130, which is a potential one-time gene therapy for Huntington’s disease
.
Neurofilament light chain (NfL) is the brain The key biomarkers of injury showed a downward trend in treated patients and returned to baseline levels.
Structural MRI data is consistent with the safety of AMT-130
.
We look forward to evaluating the safety of more patients in ongoing studies.
Biomarkers and functional data
.
"Huntington's disease (HD) is a rare genetic neurodegenerative disease that can cause motor symptoms, behavioral abnormalities, and cognitive decline, including chorea
.
The disease is an autosomal dominant genetic disease, in the first exon of the Huntington gene, there is a repeated amplification of the pathogenic CAG trinucleotide, which leads to the production and aggregation of abnormal proteins in the brain
.
Although the cause of Huntington’s disease is clear, there is currently no approved treatment to delay the onset or slow the progression of the disease
.
▲ Huntington's disease (picture source: trypanophobia.
wordpress) AMT-130 is uniQure's first clinical project focused on the central nervous system (CNS), combined with its proprietary miQURE® platform
.
UniQure’s gene therapy product candidate drug AMT-130 utilizes its proprietary miQURE™ silencing technology and consists of an AAV5 vector carrying artificial micro-RNA (micro-RNA, miRNA).
The production of mutant protein (mHTT)
.
The company believes that the use of AAV vectors to deliver miRNAs directly to the brain to knock down the huntingtin gene non-selectively represents a highly innovative and promising method for the treatment of Huntington's disease
.
The Phase I/II clinical trial of AMT-130 for the treatment of Huntington’s disease is exploring signals of safety, tolerability, and effectiveness.
It is planned to divide 26 patients with early-stage Huntington’s disease into 10 low-dose cohorts and 16 high-dose cohorts.
Cohort; patients were randomly treated with AMT-130 or sham surgery
.
This multicenter trial includes a 12-month blinded core study period and a 5-year unblinded long-term follow-up
.
Clinical progression of the first batch of patients The first four patients are a heterogeneous group, showing 41-44 CAG repeats of stage I-II early dominant disease, baseline total functional ability score of 10-13 points, total exercise score It is 7-23 points
.
AMT-130 is generally well tolerated in patients treated with lower doses (6x1012 vector genome (vg))
.
So far, no serious adverse events (SAEs) related to AMT-130 have occurred in these patients
.
Two patients receiving treatment after AMT-130 surgery, NfL immediately increased as expected and returned to baseline levels
.
In the two untreated control patients, NfL remained relatively stable
.
During the one-year follow-up, structural magnetic resonance imaging did not show any clinically significant safety findings
.
The measured values of total HTT protein and mutant HTT protein in the cerebrospinal fluid of four patients varied greatly and were inconclusive
.
To date, the safety of AMT-130 in the low-dose cohort supports continued enrollment of patients in the 6x1013vg high-dose cohort
.
So far, 19 patients have participated in the clinical trial, including 9 patients in the 16 high-dose cohort
.
The safety data update for the 10 low-dose cohort patients is expected to be announced after the patients are unblinded in the second quarter of 2022
.
After all patients in the high-dose cohort complete a one-year follow-up, it is expected that complete safety and efficacy data will be obtained from the first two cohorts of phase I/II clinical trials in the first half of 2023
.
Gene therapy strategies for rare diseases At present, there are more than 7,000 rare diseases known worldwide, accounting for about 10% of human diseases
.
Among the various rare diseases, about 80% are caused by genetic defects and are hereditary
.
The World Health Organization (WHO) defines a rare disease as a disease whose number of patients accounts for 0.
65‰ to 1‰ of the total population
.
However, due to the huge population base in our country, the number of patients with rare diseases is not uncommon
.
In recent years, gene therapy technology has made significant progress in the research of hereditary rare diseases, providing a possibility for a complete cure of the disease
.
➤In October 2021, 4D Molecular Therapeutics (4DMT), a gene drug development company based on AAV directed evolution and precise targeting technology, announced that its research gene therapy 4D-310 is 1/ Positive interim results were obtained in phase 2 clinical trials
.
This is the first clinical trial to show that a single-dose gene therapy can increase the AGA enzyme activity in Fabry disease patients to near or higher than normal levels
.
Recommended reading: Targeted AAV vector releases more potential for gene therapy! Data on the treatment of rare diseases is positive Yimai Meng broke the news ➤ In September 2021, PTC Therapeutics announced the latest five-year analysis results of its one-time gene therapy PTC-AADC.
The results showed that they suffer from aromatic L-amino acid decarboxylase deficiency (AADC) ) After receiving PTC-AADC, the children have largely recovered their motor function and cognitive skills, and these improvements are continuous
.
Recommended reading: 5 years of comprehensive improvement! Positive clinical data on gene therapy for children’s rare diseases Yimai Meng broke the news ➤In September 2021, Taysha Gene Therapies announced that its AAV9-based gene replacement therapy TSHA-102 has been awarded the title of orphan drug by the European Commission for the treatment of Rett syndrome
.
Recommended reading: For the treatment of rare diseases! An AAV9 gene therapy has just been designated as an orphan drug by the European UnionYi Mai Meng broke the news ➤ In July 2021, Abeona Therapeutics announced that its new gene therapy ABO-102 is used in the treatment of type A Sanfilippo syndrome (MPS IIIA, also known as mucopolysaccharide).
In the Phase 1/2 clinical trial Transpher A in pediatric patients with dysplasia type IIIA, positive results were obtained
.
Magnetic resonance imaging (MRI) data showed that at the 24th month, compared with untreated patients, ABO-102 had a clinically significant increase in the brain gray matter, corpus callosum, and amygdala in three patients
.
Recommended reading: Treating rare diseases! AAV gene therapy has clinical significance to increase the brain volume of children with medical science.
In May 2021, Orchard Therapeutics announced the gene therapy OTL-101 to treat patients with severe combined immunodeficiency caused by adenosine deaminase deficiency (ADA- SCID) Phase 1/2 clinical trial data
.
The results showed that the overall survival rate of ADA-SCID after receiving gene therapy for 2 and 3 years was 100%
.
Recommended reading: Treating rare diseases in children! Gene therapy shows a survival rate of 100% for fatal diseasesYi Mai Meng revealed that with the advancement of science and technology, the understanding of rare diseases is deepened, the strong support of regulatory policies, and the high attention of research and development companies, rare diseases worldwide The treatment landscape has undergone tremendous changes
.
We look forward to the emergence of more innovative therapies in the future, bringing new hope to patients with rare diseases
.
Reference materials: 1.
https:// -gene-therapy-for-the-treatment-of-huntington-s-disease/2.
http:// Recent articles recommend recent popular conference live broadcast · altaltalt
