Research and Development


Safety

In over 2000 individuals and 150,000+ doses, AIMSPRO has never elicited a serious adverse side effect and can be used as a long-term therapy without the toxicity issues which besets many other medicines. A Serious Adverse Events warning label is not required for AIMSPRO by the MHRA.

Since 85% of late stage clinical trial failures are due to safety issues, AIMSPRO carries much less risk for investors than therapies which have not been used extensively in human beings over many years



Scientific Studies

Daval International has completed preliminary animal studies, which provided a strong indication as to the positive results to be expected in a larger patient group

Contextual fear conditioning in mice was used to study the functioning of memory and the ability to learn to suppress a fear response once it has been learned. Changes in “freezing” are used as indicators of the mouse’s ability to suppress a learned fear response.


i. Mouse Study 1
  1. the Contextual Fear Conditioning test with Subtracted Values AIMSPRO-treated mice showed increased freezing (indicative of memory) compared to Naïve Serum treated mice.
  2. AIMSPRO was able to reduce average velocity significantly.
  3. AIMSPRO® significantly increased the number of BrdU and CD34+ positive cells in the hippocampus.
  4. Amyloid beta1-42 levels were significantly decreased by AIMSPRO

ii. Mouse Study 2

This study evaluated the efficacy of AIMSPRO in the Tg2576 mouse model of Alzheimer’s disease:

  1. Morris Water Maze - AIMSPRO significantly improved the mouse’s ability to learn through improved cognitive function
  2. Morris Water Maze (submerged platform) - AIMSPRO treated mice performed similarly to wild type controls and better than Tg controls
  3. Morris Water Maze (visible platform) - AIMSPRO - treated mice performed better than the naïve serum-treated Tg controls.


Alzheimer’s Disease Individual Case Studies (Humans)

Daval International has seen some positive responses in its privately treated Alzheimer patients and, as a result, the company decided to observe the effect of AIMSPRO on Alzheimer’s dementia in individual case studies. The progress of 8 individuals with Alzheimers disease who were being treated with AIMSPRO,was monitored over a 12 week treatment period. The results were encouraging and provided evidence that AIMSPRO merits full clinical testing.

Patients were treated with AIMSPRO every 3 days for 12 weeks. No other treatment parameters were altered, the patients continued to receive their usual medication and care package during this time.


i. Analysis of ADAS-cog Results

ADAS-cog tests assess a number of different skills involving cognitive functions, involving memory, perception and reasoning; a broad searching test that can take 2 hours to perform. The objective for any medication is to lower the patient’s score.

The patients achieved a 4-point change in the ADAS-Cog score over 12 weeks. This result is deemed to be clinically important.


ii. Analysis of Standardised Mini Mental State Examination (sMMSE) Results

The sMMSE test measures orientation to time and place, immediate recall, short-term verbal memory, calculation, language, and construct ability. The objective for any medication is to increase the patient’s score.

Patients’ sMMSE scores increased on average by 1.4 points. This result is held to be clinically important.


iii. Summary

The data were analysed using paired testing methods. Although the number of patients analysed is relatively small, and we have no control group to compare them to, interesting stabilisation and in some cases reversal trends were observed. Significant differences were observed in the ADAS-cog (reduction from 36.71 to 28.14 – a reduction is considered a positive result, where a change of 4 points in 6 months is considered clinically meaningful) and sMMSE (increase from 18.14 to 22.43 – an increase is considered a positive result).

NB: These results are encouraging as other recent widely publicised studies have shown efficacy by reducing the decline of scores and not reversing the scores. One such study reported statistical significance in a decline of 0.56 (MMSE) points after one year.

Studies of the different scoring systems used in Alzheimer’s Disease have shown that untreated patients decline on average by 2.3 points per annum. Recent commercial studies have reported a decline of 2.81 in a placebo arm.

Although these measures cannot be directly compared, due to different time lines and patient numbers, the data relating to Aimspro are encouraging and warrant further investigation.



The Mechanism of Action of AIMSPRO

AIMSPRO has been used to treat a large range of clinical conditions and is biologically complicated. It is understandable therefore that sometimes people find its aetiology and complexity confusing and hence question how it can be clinically effective.

i. The Benefits Of Aimspro When Administered In Humans

AIMSPRO exhibits potent and rapid anti-inflammatory effects, which appear to be a consequence of the stimulation of the HPA axis. This causes the generation of CRH and POMC peptides and consequently a very fast and strong inhibition of the production of pro-inflammatory cytokines very likely mediated by the down-regulation of the NF-kB pathway, which is responsible for controlling the DNA transcription of pro-inflammatory cytokines.

It is plausible that the anti-inflammatory, reparative and immunomodulatory properties of AIMSPRO may allow it to modify the pathologies of a complex disease such as AD via both neuro-generative and anti-inflammatory processes.


ii. Proving the Theory

In our own laboratories, we have performed prior experiments that appeared to demonstrate one of the ways that AIMSPRO functions at a molecular level. Independent third party laboratory experiments have now indicated that our proposed Mechanism of Action for AIMSPRO has validity.

In repeated experiments using larger numbers of variables and more stringent testing, AIMSPRO yielded positive results. We are now working on the expansion of these studies to test AIMSPRO at a molecular level in different cell types including cells in the brain.


Functional Assay

A functional assay is an investigational procedure for qualitatively or quantitatively assessing or measuring the presence or amount of a target entity, in this case, AIMSPRO. It is a test that is designed to measure the function, rather than simply the existence of the active substance and can demonstrate that AIMSPRO is biologically active.

The importance of a functional assay for a biological product such as AIMSPRO is extremely high in that it provides indisputable proof of its anti-inflammatory activity.

In independent laboratory tests, Daval International’s claims regarding AIMSPRO’s interaction with cells of the immune system have been validated.


Publications