Rare Neurogenetic Disorders

 

Rare Neurogenetic Disorders

 

In the field of rare neurogenetic diseases, a cross-disciplinary approach linking basic and clinical research is essential, particularly for spinocerebellar degeneration (spastic paraplegia and cerebellar ataxia) and Huntington’s disease.

Three major areas of research are being explored:

– To gain a deeper understanding of the various biological mechanisms underlying these diseases in order to develop new therapeutic strategies, including gene therapy.

– Understanding clinical variability through the identification of genetic modifiers.

– Advance research into biomarkers to identify biological changes before disease symptoms appear, during the presymptomatic phases of diseases with a delayed onset. 

There are numerous pathophysiological studies on spinocerebellar ataxias, particularly those caused by CAG triplet expansions (SCA1–7).

Indeed, it is essential to understand the mechanisms of the disease and identify biomarkers in order to demonstrate the efficacy of a treatment under study, including during the presymptomatic phase, before symptoms appear.

We have conducted a multimodal approach for SCA2 and SCA7 (CERMOI NCT04288128 / https://classic.clinicaltrials.gov/ct2/show/NCT04288128) and in collaboration with the National Institutes of Health (NIH) in the United States for SCA1 and SCA3 (READISCA NCT03487367 / https://classic.clinicaltrials.gov/ct2/show/NCT03487367).

These studies will help us precisely identify which patients to include in a clinical trial, as rare diseases require us to recruit patients in a targeted manner.

Clinical trials are underway for spinocerebellar ataxias (SCA). Some gene therapy studies involving intrathecal injection are currently in progress (very early phase, for example: NCT05160558 / https://clinicaltrials.gov/study/NCT05160558). 

 To date, there are several clinical trials for Friedreich’s ataxia involving children and adults, whose primary objectives are to enhance mitochondrial function and reduce oxidative stress (Vatiquinone, NCT05515536 / https://classic.clinicaltrials.gov/ct2/show/NCT05515536), modulating the regulatory mechanism of frataxin production (a mitochondrial matrix protein whose loss of function causes Friedreich’s ataxia in humans), stabilizing, activating, or replacing frataxin, and increasing gene expression. Gene therapy is also being considered, particularly for the treatment of cardiomyopathy. 

The number of therapeutic trials for Huntington’s disease has recently increased. The primary approach is to reduce the production of abnormal huntingtin, the protein produced by the mutated gene and responsible for the disease. A targeted approach to the abnormal protein is currently underway

(NCT05032196 / https://classic.clinicaltrials.gov/ct2/show/NCT05032196). A groundbreaking gene therapy study using a viral vector via intracerebral injection began in late 2022 (NCT05541627 / https://clinicaltrials.gov/study/NCT05541627).

In the field of rare neurogenetic diseases, a cross-disciplinary approach linking basic and clinical research is essential, particularly for spinocerebellar degeneration (spastic paraplegia and cerebellar ataxia) and Huntington’s disease.

Three major areas of research are being explored:

– To gain a deeper understanding of the various biological mechanisms underlying these diseases in order to develop new therapeutic strategies, including gene therapy.

– Understanding clinical variability through the identification of genetic modifiers.

– Advance research into biomarkers to identify biological changes before disease symptoms appear, during the presymptomatic phases of diseases with a delayed onset. 

There are numerous pathophysiological studies on spinocerebellar ataxias, particularly those caused by CAG triplet expansions (SCA1–7).

Indeed, it is essential to understand the mechanisms of the disease and identify biomarkers in order to demonstrate the efficacy of a treatment under study, including during the presymptomatic phase, before symptoms appear.

We have conducted a multimodal approach for SCA2 and SCA7 (CERMOI NCT04288128 / https://classic.clinicaltrials.gov/ct2/show/NCT04288128) and in collaboration with the National Institutes of Health (NIH) in the United States for SCA1 and SCA3 (READISCA NCT03487367 / https://classic.clinicaltrials.gov/ct2/show/NCT03487367).

These studies will help us precisely identify which patients to include in a clinical trial, as rare diseases require us to recruit patients in a targeted manner.

Clinical trials are underway for spinocerebellar ataxias (SCA). Some gene therapy studies involving intrathecal injection are currently in progress (very early phase, for example: NCT05160558 / https://clinicaltrials.gov/study/NCT05160558). 

 To date, there are several clinical trials for Friedreich’s ataxia involving children and adults, whose primary objectives are to enhance mitochondrial function and reduce oxidative stress (Vatiquinone, NCT05515536 / https://classic.clinicaltrials.gov/ct2/show/NCT05515536), modulating the regulatory mechanism of frataxin production (a mitochondrial matrix protein whose loss of function causes Friedreich’s ataxia in humans), stabilizing, activating, or replacing frataxin, and increasing gene expression. Gene therapy is also being considered, particularly for the treatment of cardiomyopathy. 

The number of therapeutic trials for Huntington’s disease has recently increased. The primary approach is to reduce the production of abnormal huntingtin, the protein produced by the mutated gene and responsible for the disease. A targeted approach to the abnormal protein is currently underway

(NCT05032196 / https://classic.clinicaltrials.gov/ct2/show/NCT05032196). A groundbreaking gene therapy study using a viral vector via intracerebral injection began in late 2022 (NCT05541627 / https://clinicaltrials.gov/study/NCT05541627).