Huntington’s disease

Huntington’s Disease: A Neurodegenerative Disorder with a Complex Journey

Imagine a journey through the human body, where every step is marked by increasing difficulty and decline. This is what Huntington’s disease (HD) does to its victims. HD is a neurodegenerative disorder that affects physical abilities, mental functions, and emotional well-being. It’s like a slow-moving storm, gradually eroding the very essence of who we are.

Understanding the Symptoms

HD manifests through a triad of motor, cognitive, and psychiatric symptoms. These can be noticeable between ages 30-50 but may begin at any age. Think of it as a three-pronged attack on the body: chorea (jerky movements), rigidity, abnormal posturing, cognitive decline, dementia, anxiety, depression, and compulsive behavior. Each symptom is like a piece of a puzzle that gradually comes together to form a picture of what HD looks like in its full glory.

The Genetic Underpinning: A Tragic Inheritance

Everyone has two copies of the huntingtin gene (HTT), which codes for the huntingtin protein. The gene contains a repeated section called a trinucleotide repeat expansion. If this section is present in a healthy gene, it may increase the risk of producing a defective gene that causes HD. The length of this repeated section affects the severity of the disease and its penetrance.

The HTT gene contains a sequence of three DNA bases (CAG) repeated multiple times, known as a trinucleotide repeat. A series of these repeats results in the production of a chain of glutamine, known as a polyglutamine tract. Typically, people have fewer than 36 repeated glutamines, which results in the production of normal huntingtin protein. However, a sequence of 36 or more glutamines results in the production of mutant huntingtin (mHtt), which increases the decay rate of certain types of neurons and causes the disease symptoms.

Diagnosis: A Journey Through Uncertainty

Diagnosing HD involves genetic testing, which raises ethical debates about testing age, parental consent, and confidentiality. The test can confirm the presence of an expanded copy of the trinucleotide repeat in the HTT gene. It can predict the risk of developing the disease, with different cutoffs indicating full penetrance (40+ CAG repeats), incomplete or reduced penetrance (36-39 repeats), and no risk.

Testing before onset of symptoms can aid career and family decisions but has no treatment and carries anxiety, stress, and risk of suicide for positive results. Genetic counseling provides information, advice, and support. Preimplantation genetic diagnosis (PGD) and prenatal testing are available for at-risk individuals. It has no procedure-related risk of miscarriage.

Treatments: A Fight Against the Symptoms

While there is no cure for HD, treatments can relieve symptoms and improve quality of life. Physical therapy, occupational therapy, speech therapy, nutrition management, and palliative care are available to reduce severity. Tetrabenazine was approved for treatment of chorea in HD in the EU and US. Other drugs that help reduce chorea include antipsychotics, benzodiazepines, and antiparkinsonian medications.

Support Organizations: A Beacon of Hope

Support organizations, such as the Hereditary Disease Foundation (HDF), have played a key role in supporting research into HD. The discovery of the HD gene was led by research teams in Venezuela, including Dr. Milton Wexler and his daughter Nancy Wexler. At roughly the same time the Huntington’s Disease Foundation (HDF) was formed after Woody Guthrie’s death, Marjorie Guthrie helped found the committee to Combat Huntington’s Disease, which later became the Huntington’s Disease Society of America.

Since then, support and research organizations have formed globally, including umbrella organizations like the International Huntington Association and the European HD network. Many organizations hold annual awareness events, such as National Huntington’s Disease Awareness Day in the US.

The Future: A Race Against Time

Research into the mechanism of HD is focused on identifying the functioning of Htt and understanding brain pathology. Research uses in vitro methods, genetically modified animals, human volunteers, and animal models to study disease progression and development. Disease-modifying strategies include reducing mutant huntingtin protein levels, improving neuronal survival, and replacing lost neurons.

The Cure Huntington’s Disease Initiative Foundation (CHDI) is the largest funder of research globally, aiming to find and develop drugs that slow HD progression. CHDI collaborates with academic and commercial laboratories and funds research initiatives providing publications.

Condensed Infos to Huntington

The journey of HD is a complex one, filled with challenges and uncertainties. But as research progresses and support networks grow stronger, the hope for better treatments and ultimately a cure remains alive. The fight against this devastating disease continues, driven by the resilience of those affected and the dedication of researchers and supporters.