Treatment for patients with GM2 Gangliosidosis – which consists of Tay-Sachs disease and Sandhoff disease – has often been symptomatic and supportive. However, a new therapy shows promise in benefiting patients even further. According to the Jerusalem Post, IB1001, developed by biopharmaceutical company IntraBio, has resulted in positive clinical trial results within the IB1001-202 trial.
IB1001
So what exactly is IB1001? According to IntraBio, the drug is part of the IB1000 series:
a set of orally administered, modified amino acids (N-Acetyl-Leucine) characterized by a well-established safety and tolerability profile. In compassionate-use clinical trials, IB1000s have demonstrated statistically significant efficacy for a broad spectrum of lysosomal storage disorders (LSD) and rare and common neurodegenerative diseases.
Thus far, IB1001 actually initially showed benefits for patients with Niemann-Pick disease type C (NPC). See the positive interim results here.
However, researchers soon believed that the treatment could also benefit patients with Tay-Sachs disease and Sandhoff disease. IB1001 is orally administered. In this case, the therapy is first dissolved in water and later given to patients. While the clinical trial was delayed, due in part to COVID-19, researchers are now beginning to see its impact. During the trial, researchers also determined that IB1001 was relatively safe and well-tolerated.
Currently, treatments for Tay-Sachs disease and Sandhoff disease are limited. Thus, if IB1001 shows benefit, it could fulfill an unmet need within this patient population. Data from the trial will be published in the upcoming months.
Tay-Sachs Disease
HEXA gene mutations cause Tay-Sachs disease, a rare and fatal inherited lysosomal storage disease. Normally, HEXA plays a role in creating an enzyme which breaks down fatty substances called gangliosides. But gene mutations cause enzyme deficiencies, which allow gangliosides to accumulate within the brain and central nervous system (CNS). Ultimately, this accumulation is toxic, causing nerve destruction, organ and tissue damage, and loss of bodily functions. Tay-Sachs disease disproportionately affects those of Ashkenazi Jewish, French Canadian, or Cajun descent.
There are juvenile and late-onset adult forms of Tay-Sachs disease. Typically, within the juvenile form, patients show symptoms by age 5, and the disease is fatal by mid-teens. In the adult-onset form, cognitive and physical deterioration occurs, though the condition may not be fatal.
However, the most common form of Tay-Sachs disease is infant-onset. In some cases, Tay-Sachs may be diagnosed in the womb through screening measures; for others, symptoms appear around 6 months old. Regardless, this form is usually fatal within the first few years of life. Symptoms include:
- Exaggerated startle response
- “Floppy” muscle tone
- Developmental regression (loss of previously acquired skills)
- Low energy
- Muscle stiffness and paralysis
- Cherry red spots in the eyes
- Vision and hearing loss
- Seizures
- Dementia
Sandhoff Disease
Sandhoff disease, a lipid storage disorder, results from gene mutations for a beta subunit of hexosaminidase B enzyme. As a result, gangliosides accumulate within the CNS, causing toxicity and other issues. Sandhoff disease predominantly affects those of Lebanese, Metis Indian, and Creole descent. Symptoms typically appear within the first 3-6 months following birth. Unfortunately, this condition comes with a poor prognosis and is often fatal within 3 years. When symptoms appear, these include:
- Lethargy
- Difficulty feeding
- Exaggerated startle reflex
- Muscle weakness
- Loss of muscle coordination
- Cherry-red spots in the eyes
- Enlarged spleen
- Motor delays
- Developmental and mental regression
- Heart murmurs
- Vision loss
- Seizures
