Huntington’s disease (HD) is a rare and fatal hereditary disorder that progressively destroys the nerve cells in the brain.

It is an autosomal dominant inheritance disorder, which means that if one parent has the disease, the offspring have a 50% chance of inheriting it. HD was first described by George Huntington in 1872, and since then, scientists have been trying to break the code of HD.

What is HD?

HD is a genetic disorder that causes the progressive degeneration of nerve cells in the brain, which leads to the gradual decline of a person’s motor, cognitive, and psychiatric functions.

The disease affects both males and females, and it usually appears in people’s 30s or 40s, although it can start earlier or later in life. HD is caused by a mutation in the Huntingtin (HTT) gene on chromosome 4, which leads to the production of a toxic protein called mutant huntingtin (mHTT).

The accumulation of mHTT in the brain cells leads to their dysfunction and death, which, in turn, causes the symptoms of HD.

Symptoms of HD

The symptoms of HD vary from person to person and depend on the stage of the disease. However, they can be grouped into three categories: motor, cognitive, and psychiatric symptoms.

Motor symptoms include involuntary jerking movements (chorea), stiffness, slowed movements, difficulty with balance and coordination, and difficulty with swallowing. Cognitive symptoms include difficulty with concentration, memory loss, and impaired judgment. Psychiatric symptoms include depression, anxiety, irritability, and apathy.

Diagnosis of HD

The diagnosis of HD is based on a combination of clinical, genetic, and neuroimaging tests. The clinical diagnosis is based on the presence of the characteristic symptoms of HD, such as chorea, cognitive impairment, and psychiatric symptoms.

The genetic diagnosis is based on the detection of the HTT gene mutation through a blood test or a DNA analysis. The neuroimaging tests, such as magnetic resonance imaging (MRI) or positron emission tomography (PET), can detect the structural and functional changes in the brain associated with HD.

Treatment of HD

Currently, there is no cure for HD, and the available treatments can only alleviate the symptoms of the disease. The treatment of HD is multidisciplinary and includes medications, physical therapy, speech therapy, and occupational therapy.

The medications used to treat HD target the symptoms of the disease, such as chorea, depression, anxiety, and sleep disorders. The physical therapy can improve the patient’s motor skills, while the speech therapy can enhance their communication abilities. The occupational therapy can help the patient to maintain their independence and improve their quality of life.

Breaking the Code of HD

The code of HD remained unbroken for many years, but recent research breakthroughs have shed light on the disease’s mechanisms, diagnosis, and treatment.

One of the most significant breakthroughs was the identification of the HTT gene mutation that causes HD, which allowed for the development of genetic tests and genetic counseling for HD families. Moreover, the discovery of the mHTT protein’s toxic effects on brain cells has opened new avenues for drug development.

Gene Silencing Therapy

One of the most promising approaches to treat HD is gene silencing therapy, which aims to reduce the production of the mHTT protein by suppressing the expression of the HTT gene.

There are several gene silencing strategies under development, including antisense oligonucleotides (ASOs), RNA interference (RNAi), and genome editing. ASOs are small RNA molecules that bind to the HTT mRNA and prevent it from being translated into the mHTT protein. RNAi works similarly, but it uses short interfering RNAs (siRNAs) instead of ASOs.

Genome editing uses CRISPR-Cas9 technology to precisely modify the HTT gene and correct the mutation.

Stem Cell Therapy

Another innovative approach to treat HD is stem cell therapy, which aims to replace the damaged brain cells with healthy ones derived from stem cells.

Stem cells are unspecialized cells that have the potential to develop into any type of cell in the body. There are several types of stem cells, including embryonic stem cells, induced pluripotent stem cells, and adult stem cells.

The use of embryonic stem cells is controversial, but the other types of stem cells have shown promising results in preclinical and clinical studies.

Conclusion

Huntington’s disease is a devastating disorder that affects millions of people worldwide. However, the recent breakthroughs in our understanding of the disease’s mechanisms, diagnosis, and treatment give hope for a cure.

Gene silencing therapy and stem cell therapy are two of the most promising approaches to treat HD, but there are still many challenges to overcome, such as safety, efficacy, and affordability. Nonetheless, the efforts to break the code of HD are ongoing, and we may see a cure for this disease in the near future.