A recent drug study “offers hope for Alzheimer’s treatment” according to The Times . The newspaper reports that after three months’ treatment with a new drug called CPHPC, all of the SAP protein linked to Alzheimer’s had been cleared from the brains of patients with milder forms of the disease.
Despite the reported success of the drug, this small pilot study was not actually designed to look at the clinical effects of the drug on Alzheimer’s disease. It followed five people for 16 weeks and its main aim was to look at the drug’s safety and levels of the SAP protein in the fluid surrounding the brain and spinal cord. However, the drug does show some promise in that the patients did not show any deterioration during this period. The results were described as “very encouraging” by one of the researchers.
The study’s short length and the lack of a control group mean that it is not clear if the treatment affects cognitive decline in Alzheimer’s. Larger studies with control groups are needed to determine whether this treatment can benefit patients with the disease.
Where did the story come from?
This research was conducted by Dr Simon Kolstoe, Professor Mark Pepys and colleagues from University College London Medical School and the University of Cambridge. The study was funded by the Department of Health’s National Institute for Health Research Biomedical Research Centres funding scheme, the Medical Research Council, the Walters Kundert Trust, the Royal Society and the Alzheimer Research Trust.
One of the authors is the inventor of patents relating to SAP and CPHPC that are owned by Pentraxin Therapeutics Ltd, a company in which he and two other authors own shares.
The study was published in the peer-reviewed scientific journal, Proceedings of the National Academy of Science of the United States of America.
What kind of scientific study was this?
This was a small, unblinded case series looking at the safety of the drug CPHPC in people with Alzheimer’s disease, and its effects on the levels of the SAP protein in the fluid surrounding the brain and spinal cord (cerebrospinal fluid).
SAP is known to bind to and stabilise amyloid fibrils (tangles), which form the typical type of deposits found in the brains of people with Alzheimer’s. SAP is found in the cerebrospinal fluid, amyloid deposits and typical protein tangles found in the nerve cells in the brains of people with Alzheimer’s disease.
The researchers thought that SAP could be playing a role in the degeneration of the nerves that occurs in Alzheimer’s, and that by stopping it from binding to amyloid tangles it might affect the progression of the disease. The drug CPHPC was developed to stop SAP binding to amyloid tangles and remove it where it had already bound.
The researchers enrolled five patients aged 53 to 67 years old with mild-to-moderate probable Alzheimer’s disease. Details of how the disease was diagnosed were not reported in the paper.
The researchers injected 60 milligrams (mg) of CPHPC under the skin of these patients three times a day for 12 weeks. They measured the concentration of SAP in the cerebrospinal fluid of the patients before CPHPC treatment, every four weeks during treatment, and four weeks after treatment had finished.
The researchers also measured the levels of CPHPC and other chemicals in blood and cerebrospinal fluid during the study.
At the start and end of the study, patients had MRI brain scans and had their cognitive abilities measured using standard tests called the MMSE, ADAS-Cog and CIBIC+. The researchers also assessed whether the patients experienced any adverse effects of the drug treatment.
The researchers carried out further experiments looking at how CPHPC interacts with SAP in solutions, and how the compounds formed behave when injected into mice.
What were the results of the study?
On the MMSE, scores over 27 (out of 30) are effectively normal; 20-26 indicates some cognitive impairment; 10-19 indicates moderate to severe cognitive impairment and below10 very severe cognitive impairment. The patients’ average MMSE score at the start of the study was 21, suggesting that they had mild cognitive impairment.
The researchers report that none of the five patients experienced any adverse effects of CPHPC treatment, other than discomfort during the injection that faded with time.
The concentration of SAP in the patients’ cerebrospinal fluid decreased from an average of about 32mg per litre before starting treatment, to 0.25mg per litre during treatment. The levels then rose to close to pre-treatment levels after stopping the CPHPC injections.
The patients’ cognitive abilities before and after CPHPC treatment did not differ, and the researchers reported that there were no structural changes visible in the patients’ brain MRI scans. There were no changes in the concentrations of fragments of the amyloid protein or other related proteins in the cerebrospinal fluid during the study.
What interpretations did the researchers draw from these results?
The researchers conclude that the study shows CPHPC can cause depletion of SAP from the cerebrospinal fluid of patients with Alzheimer’s disease and that this treatment is safe.
They say that their results support the need for longer-term studies of the clinical effects of CPHPC in this population.
What does the NHS Knowledge Service make of this study?
This small and short-term pilot study has shown that the protein SAP can be depleted from the cerebrospinal fluid patients with probable Alzheimer’s disease.
However, the study did not report on the effects of the treatment on any SAP in existing plaques and tangles in the brains of the patients or on the formation of new plaques.
Also, as the authors acknowledge, this study was also too short to determine whether the treatment has any effect on cognitive decline. Larger studies with control groups, (ideally randomised controlled trials) are needed to determine whether this treatment can offer any benefits for patients with Alzheimer’s disease.