A novel clinical trial is underway at Macquarie University, testing a combination of doxycycline, a common antibiotic, and ambroxol, a cough medicine, as a potential treatment for Dementia with Lewy Bodies (DLB). Led by Professor Simon Lewis, the Phase II trial aims to target the underlying mechanisms of DLB, potentially slowing or even halting its progression.
Addressing a Critical Unmet Need in Dementia Care
DLB is the second most prevalent form of dementia after Alzheimer's disease, characterized by a rapid and aggressive progression. It shares symptomatic overlap with Parkinson's disease, including cognitive and motor impairments, mood changes, sleep disturbances, hallucinations, and loss of smell. According to Professor Lewis, approximately 20% of Australian dementia patients are likely to have DLB, with many cases misdiagnosed due to the similarity in symptoms with other conditions. The misdiagnosis can lead to inappropriate treatments and a lack of critical support, significantly impacting the patient's quality of life and prognosis.
Targeting Alpha-Synuclein Aggregation
The rationale behind the dual-drug approach lies in addressing the abnormal protein build-ups associated with neurodegenerative diseases, including DLB. Lewy bodies, composed of aggregated alpha-synuclein protein, are a hallmark of DLB and Parkinson's disease. In vitro studies have demonstrated that doxycycline can prevent the formation of these damaging alpha-synuclein clumps. Simultaneously, ambroxol has been shown to enhance the production of an enzyme responsible for clearing these protein aggregates.
Trial Design and Patient Involvement
The Phase II clinical trial involves participants taking five pills daily (three in the morning and two at night) over a six-month period. The study employs a placebo-controlled design, with three out of four participants receiving the active treatment and one out of four receiving a placebo. Prior to the intervention, participants undergo baseline blood tests, medical assessments, and cognitive evaluations. Follow-up testing is conducted after the intervention to assess the treatment's impact. Bruce Wilson, a 75-year-old DLB patient diagnosed nearly ten years ago, is among those participating in the trial. His wife, Judith, highlighted the importance of participating in the trial to potentially help others affected by this cruel disease, even if it may not directly benefit Bruce.
Diagnostic Challenges and Future Directions
Professor Lewis emphasizes the importance of early and accurate diagnosis of DLB. He notes that until recently, definitive diagnosis was only possible post-mortem. However, blood tests are currently under development to aid in diagnosing the disease in living patients. Professor Lewis also points to three telltale symptoms that can assist in confirming DLB in dementia patients: acting out dreams, loss of smell, and physical changes such as a shuffling gait or tremor. Individuals experiencing these symptoms may be eligible to participate in the clinical trial, offering hope for improved treatment options for this debilitating condition.
