Disease

Brief Summary

Huntington disease is an autosomal dominant disorder. Only one copy of the altered HTT gene is needed for the disease to be present. Huntington's disease (HD) is a progressive genetic brain disorder. This disease causes changes in the central area of the brain, which affect movement, mood and thinking skills.

Source

Image:

Person with Huntington's DIsease

Frequency

It affects an estimated 3 to 7 per 100,000 people of European ancestry. The disorder appears to be less common in some other populations, such as the Japanese, Chinese, and African descent. About 30,000 people in the United States have Huntington’s disease and another 200,000 are at risk of developing the condition.

To date, there are only two reported, genetically proven familial HD cases in the Philippines.

Inheritance

Huntington's disease is an autosomal dominant disorder. When the number of CAG repeats reaches 41 or more, the disease is fully penetrant. Incomplete penetrance can occur with 36 to 40 repeats. The number of repeats accounts for approximately 60% of the variation in age at onset, with the remainder determined by modifying genes and environment early-onset Huntington's is almost always inherited from the father, but there are cases where the late-onset disease is more often inherited from the mother

History of Disease

The first ever recorded data of this disease was made in 1842, in a letter written by Charles Oscar Waters and published in Practice of Medicine. However, In 1872, George Huntington gave the first complete description of the disease based on his studies of several generations of one family who exhibited similar symptoms, thus it was called the "Huntington's Disease".

Brief Summary

History of Disease

Pathogenesis

Achondroplasia is caused by a mutation in the FGF3 gene in chromosome 4 at 4p 16.3. This mutation causes a decreased production of fibroblast growth factor receptor 3 which is crucial in the conversion of cartilage into bone which is vital in the proper development of a person. This mutation is inherited in an autosomal dominant manner. More than 80 percent of people with achondroplasia have parents with normal characteristics and are born with achondroplasia due to a recent (de novo) gene modification (mutation).

Pathogenesis

The disease is caused by mutation in a gene located on chromosome 4. The disease is caused by a defective HTT protein, which is made from an HTT gene(Huntingtin gene) with an increased number of CAG tri nucleotide repeats within the gene. The abnormal version of HTT gene contains more than 26 repeats, while the normal HTT gene has 26 or even fewer CAG repeats. If there are continuous repeats, then it will give rise to a protein that is harmful to cells. Thus, there will be a production of a long huntingtin protein, if there is an additional repeat to the CAG segments. The elongated protein is cut into smaller, toxic fragments that bind together and accumulate in neurons, disrupting the normal functions of these cells. The dysfunction and eventual death of neurons in certain areas of the brain underlie the signs and symptoms of Huntington's disease.

Image:

Mutated chromosome by Huntington's Disease

Source

HUNTINGTON'S DISEASE

Symptoms

Depression

Difficulty in concentrating

Memory Lapse

Clumsiness

Mood Swings

Problem with communicating and breathing

Difficulty moving

Social Concerns

Jona et al. (2017) conducted a study to assess the family functioning in Huntington's disease families. Over 61 participants were used in the study, 23 family members, and 38 HD gene-expanded participants). Thus, the researchers used McMaster Family Assessment Device (FAD; Epstein, Baldwin and Bishop, 1983), in order for them to provide scores for seven domain functions such as communication, problem solving, behavior, affective responsiveness, roles, and general family functioning. Their results have shown that the most commonly reported disrupted domain for family members was Affective involvement and Communication (both 52.2%). While for the HD participants, the disrupted domain was Affective Involvement (39.5%), followed by General family functioning (36.8%). Moreover, symptomatic Huntington's Disease participants were reported to be more disrupted in Problem Solving than pre-symptomatic Huntington's disease participants. All domains have shown a moderate very good agreement, which results in an agreement between pre-symptomatic and asymptomatic HD participants and their family members. In terms of family members, rated Communication as more disrupted than their HD affected family members. Lastly, their study focuses on the target areas of emotional engagement, communication skills, and problem solving in family interventions in Huntington's Disease.

Treatment

Doctors examine the individual and test things such as their thinking, balance and walking ability. MRI scan or image test is sometimes used in determining the presence of HD.

Currently, there is no cure for Huntington’s Disease. However, there are treatments that are used in order for this disease to be mitigated.

For symptomatic therapies:

Motor Symptoms

Tetrabenzene
Deutetrabenazine
Riluzole
Amantadine

Behavior Symptoms

Antidepressant
Antipsychotics
Benzodiazepines

Disease Modifying Therapies:

Immuno-based pharmacological

therapies

Minocycline
Laquinimod
Antibodies

Stem Cell Therapies

MSCs
ESCs
NPCs

Image:

Physical therapy with a person with Huntington's Disease

Source

Clinical Trials

PRidopidine's Outcome on Function in Huntington Disease, PROOF- HD

Intervention:

Drug: Pridopidine/ Placebo

Phase:

Phase 3

Procedure:

ROOF-HD is a Phase 3 clinical trial looking into the drug pridopidine as a possible treatment for Huntington's disease. Up to 480 participants with early-stage HD from throughout the world will be included in this study. Participants must be 25 years old or older and have been diagnosed with early-stage adult-onset HD. Participants will be randomly assigned to receive either a 45 mg pridopidine oral capsule or a placebo twice daily during the trial. The research will span 65 to 78 weeks, with an optional open-label extension phase for individuals who want to continue treatment after that. Pridopidine was previously studied in other clinical trials (PRIDE-HD and OPEN-HART), which showed that it was overall well-tolerated by patients.

Goal:

The goal is to evaluate the efficacy and safety of pridopidine 45mg twice daily (BID) in patients with early stage manifest Huntington Disease (HD).

Further details at:

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04556656. https://clinicaltrials.gov/ct2/show/study/NCT04556656?cond=Huntington%27s+Disease&draw=2&rank=1

Title:

Clinical Trials

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