History of Huntington's disease in Timeline

Huntington's disease (HD) is a fatal, inherited neurodegenerative disorder characterized by a triad of progressive psychiatric, cognitive, and motor symptoms. Initial symptoms often involve subtle mood or psychiatric changes, preceding motor impairments like lack of coordination and unsteady gait. The disease progressively damages the basal ganglia, leading to chorea, a hyperkinetic movement disorder marked by involuntary, dance-like movements. Physical abilities deteriorate, impacting speech and coordination. Cognitive decline results in dementia, depression, apathy, and impulsivity. Symptom onset typically occurs around age 40, though juvenile HD can manifest before age 20 with Parkinson's-like symptoms. The disease tends to appear earlier in subsequent generations.

1906: Johan Christian Lund dies

In 1906, Johan Christian Lund, who produced an early description of Huntington's Disease, dies.

1910: Charles Davenport proposes eugenic measures for HD

In 1910, Charles Davenport controversially proposed compulsory sterilization and immigration control for people with certain diseases, including Huntington's disease, as part of the eugenics movement.

1932: P. R. Vessie popularizes theory of HD progenitors

In 1932, P. R. Vessie popularized the idea that three brothers who left England in 1630 bound for Boston were the progenitors of Huntington's disease in the US, contributing to misunderstandings and prejudice about the disease.

1968: Hereditary Disease Foundation (HDF) founded

In 1968, The Hereditary Disease Foundation (HDF) was created by Milton Wexler, after his wife Leonore Sabin was diagnosed with Huntington's disease.

1968: Dr. Milton Wexler Inspired to Start the Hereditary Disease Foundation

In 1968, after experiencing HD in his wife's family, Dr. Milton Wexler was inspired to start the Hereditary Disease Foundation (HDF), with the aim of curing genetic illnesses by coordinating and supporting research.

1979: US-Venezuela Huntington's Disease Collaborative Project started

In 1979, the US-Venezuela Huntington's Disease Collaborative Project began, aiming to locate the genetic cause of Huntington's disease.

1983: Approximate location of causal gene found

In 1983, a causal gene for Huntington's disease was approximately located as part of the US-Venezuela Huntington's Disease Collaborative Project.

1986: Predictive testing for Huntington's disease available via linkage analysis

In 1986, Predictive testing for Huntington's disease became available via linkage analysis.

1990: Start of UK prevalence study

In 1990, A study on the prevalence of Huntington's Disease in the UK started.

1993: Gene Precisely Located at Chromosome 4

In 1993, the gene for Huntington's disease was precisely located at chromosome 4 (4p16.3) through the US-Venezuela Huntington's Disease Collaborative Project. The project focused on isolated Venezuelan villages and involved over 18,000 people.

1993: Discovery of the genetic basis of Huntington's disease

In 1993, the genetic basis of Huntington's disease was discovered by an international collaborative effort led by the Hereditary Disease Foundation.

1993: Predictive testing available via direct mutation analysis

Since 1993, Predictive testing for Huntington's disease has been available via direct mutation analysis.

1996: Transgenic mouse developed

In 1996, a transgenic mouse model for Huntington's disease was developed, enabling larger-scale experiments due to faster metabolism and shorter lifespans compared to humans.

1997: Discovery of mHtt fragments misfolding

In 1997, it was discovered that mHtt fragments misfold, leading to the discovery of nuclear inclusions they cause, which spurred further research into the proteins involved with the disease and potential drug treatments.

2000: Tetrabenazine approved in the EU for chorea treatment

In 2000, tetrabenazine was approved in the EU for the treatment of chorea in Huntington's disease.

2006: CHDI Foundation spends $50 million on research

In 2006, the CHDI Foundation, formerly known as the High Q Foundation, allocated $50 million to Huntington's disease research. The foundation collaborates with academic and commercial laboratories globally, overseeing and managing research projects as well as funding.

2008: Tetrabenazine approved in the US for chorea treatment

In 2008, tetrabenazine was approved in the United States for the treatment of chorea in Huntington's disease, marking the first approved treatment for the disease in the U.S.

2010: End of UK prevalence study

In 2010, A study on the prevalence of Huntington's Disease in the UK ended.

2013: Epidemiological study of Huntington's disease prevalence in the UK

In 2013, an epidemiological study of the prevalence of Huntington's disease in the UK between 1990 and 2010 found that the average prevalence for the UK was 12.3 per 100,000.

2015: First gene silencing trial begins and mutant huntingtin is detected

In 2015, the first gene silencing trial involving humans with Huntington's disease commenced, testing the safety of IONIS-HTTRx, produced by Ionis Pharmaceuticals and led by UCL Institute of Neurology. Also in 2015, mutant huntingtin was detected and quantified for the first time in cerebrospinal fluid from Huntington's disease mutation-carriers using a novel "single-molecule counting" immunoassay.

2017: Deutetrabenazine (Austedo) approved by the FDA

In 2017, deutetrabenazine, a heavier form of tetrabenazine medication, was approved by the FDA for the treatment of chorea in Huntington's disease and marketed as Austedo.

2017: UK Insurance agreement on genetic test disclosure

In 2017, the agreement between the United Kingdom's insurance companies and the Department of Health and Social Care, stating customers would not need to disclose predictive genetics tests to them, was in effect. The agreement explicitly excluded the government-approved test for Huntington's when writing policies with a value over £500,000.

2019: Phase 3 trial of tominersen begins and Uniqure gene therapy trial starts

In 2019, a phase 3 trial of IONIS-HTTRx, renamed tominersen and sponsored by Roche Pharmaceuticals, began. In 2019, a huntingtin-lowering gene therapy trial run by Dutch pharmaceutical company Uniqure began, and several trials of orally administered huntingtin-lowering splicing modulator compounds have been announced.

2020: 197 clinical trials underway or completed

In 2020, there were 197 clinical trials related to varied therapies and biomarkers for Huntington's disease listed as either underway, recruiting or newly completed. Compounds trialled that have failed to prevent or slow the progression of Huntington's disease include remacemide, coenzyme Q10, riluzole, creatine, minocycline, ethyl-EPA, phenylbutyrate and dimebon.

2021: Phase 3 trial of tominersen halted

In 2021, the phase 3 trial of tominersen, which had begun in 2019, was halted after the safety monitoring board concluded that the risk-benefit balance was unfavourable.

2023: Valbenazine (Ingrezza) Approved by FDA

In 2023, valbenazine (Ingrezza) was approved by the FDA for the treatment of Huntington's disease chorea.

2025: Uniqure gene therapy trial reports preliminary results

In 2025, researchers at University College London reported preliminary results from a Uniqure huntingtin-lowering gene therapy trial, showing a 75% slowing of clinical progression over three years. The full data have not yet been peer-reviewed nor published.

2025: Study examining the mechanism behind the onset of symptoms published

In 2025, scientists affiliated with Harvard and MIT published a study examining the mechanism behind the onset of symptoms. The study found that the length of the repeated trinucleotide sequence increases with age due to accumulated errors in DNA mismatch repair processes after transcription, and that this becomes toxic once the sequence expands beyond 150 repeats.

2025: Votoplam through Phase 2 trial

In 2025, votoplam is through Phase 2 trial. Gene splicing techniques are being looked at to try to repair a genome with the erroneous gene that causes HD, using tools such as CRISPR/Cas9.