AF-16 peptide

AF-16 peptide is a synthetique peptide.  The peptide is a part of the endogenaus protein AF

Indications

AF-16® can be administered orally, nasally, topically in the eye, topically on mucosa surfaces, intravenously, subcutaneously and topically on the skin. 

In animal studies it has been shown that AF-16® has positive effects on disorders of the central nervous system like cerebral oedema and stroke. Promising effects with AF-16® have also been demonstrated in reducing increased intraocular pressure, glaucoma. 

The studies show that AF-16® has neuroprotective properties, improves survival of neurons after cerebral trauma, reduces posttraumatic inflammation and oedema and reduces activation of microglia and astrocytes. 

AF-16® has very powerful and unique effects in humans. Animal studies in glaucoma have shown that AF-16® is equivalent to other drugs. Moreover AF has no side effects! 

AF-16® has also shown significant effects in experimental studies of breast and prostate cancer. The peptide can be administered in addition to chemotherapy and radiation, which means that much more of the cytotoxic drug reaches the tumour cell, which then dies. 

Strong effects have also been shown in various head traumas, including cerebral haemorrhage, stroke and direct skull fractures. The AF-peptide provides for example, a three times wider treatment window for stroke compared to current therapies. In a study of mice with virus induced encephalitis (brain inflammation) the survival rate was 100%, which is unique! This has led to interest from WHO. 

Other uses have also been identified and a number of animal studies have been made.


Studies

AF-16® can be administered orally, nasally, topically in the eye, topically on mucosa surfaces, intravenously, subcutaneously and topically on the skin. 

In animal studies it has been shown that AF-16® has positive effects on disorders of the central nervous system like cerebral oedema and stroke. AF-16® has also demonstrated promising treatment effects in reducing increased intraocular pressure, glaucoma. 

The studies show that AF-16® has neuroprotective properties, improves survival of neurons after cerebral trauma, reduces posttraumatic inflammation and oedema and reduces activation of microglia and astrocytes. 

AF-16® has very powerful and unique effects in humans. Animal studies in glaucoma have shown that AF-16® is equivalent to other drugs. Moreover AF has no side effects! 

AF-16® has also shown significant effects in experimental studies of breast and prostate cancer. The peptide can be administered in addition to chemotherapy and radiation, which means that much more of the cytotoxic drug reaches the tumour cell, which then dies. 

Strong effects have also been shown in various head traumas, including cerebral haemorrhage, stroke and direct skull fractures. The AF-peptide provides for example, a three times wider treatment window for stroke compared to current therapies. In a study of mice with virus induced encephalitis (brain inflammation) the survival rate was 100%, which is unique! This has led to interest from WHO. 

Other uses have also been identified and a number of animal studies have been made. Not surprisingly, some of the largest global pharmaceutical companies have expressed interest in the AF-peptide. 

AF-16® and Neuroprotection

Brain oedema, haemorrhage and obstruction or derangement of the blood-brain barrier can lead to increased intracranial pressure (ICP) that can damage brain function, resulting in inflammation with possible persistent neurological and psychiatric malfunctions. The extent of brain damage is related to the severity and length of ICP increase. 

In humans, blast –related brain injuries are known to cause brain oedema, vasospasm and intracranial haemorrhage. Current treatment alternatives for reducing ICP are not indicated at low levels (less than 25 mm Hg). However, the effects of exposure to low and mild blast levels of brain injury is of increased interest due to the involvement of many soldiers in wars such as the Afghani war, where soldiers are often subjected to traumatic brain injury without damage to the head. 

It has been reported in a rat model study that low blast overpressure in a shock tube resulted in impaired cognitive functions and caused an elevated ICP in a dose-dependent manner (Hoane, Kaplan and Ellis, Brain Res, 2006; 1125: 185-193) link

In the studies of AF-16® several different brain damage models have been used in two species in order to study diffuse neurotrauma, focal neurotrauma, neurotoxic agents and infections. 

The low blast overpressure experiment by Hoane et al has been repeated with rats fed a diet with 20% of an AF-inducing feed, SPC-Flakes® (Säljö, Svensson, Mayorga et al, J Neurotrauma, 2009; 27: 1345-1352) link. The study showed that the addition of SPC-Flakes® prevented the impairment of cognitive function and dramatically reduced the ICP elevation. 

AF-16® normalizes the high intracranial pressure (ICP) two days after a head trauma.

Conclusions AF-16® and Neuroprotection

  • AF-16® is beneficial for the treatment of stroke, brain trauma, intracranial hypertension, infections, glaucoma and high intraocular pressure (IOP)
  • AF-16® has a reproducible, rapid onset of action and duration
  • AF-16® is neuroprotective
  • AF-16® can be used several hours after trauma
  • No local or systemic side effects 

Conclusions AF-16® and Neurotoxic agents

  • AF-16® treatment reduced degenerative and reactive alterations in hippocampus, caused by kainic acid - an animal model of Parkinson’s disease
  • AF-16® reduced the loss of nerve cells in the retina and the reactive changes in the optic nerve after kainic acid - a model of glaucoma eye damage 

AF and Brain inflammation

In an American study of AF and encephalomyelitis (Davidson and Hickey, J Leukocyte Biology, 2004; 76: 835-844 link) the authors concluded that Antisecretory Factor (AF) expression is regulated by inflammatory mediators and influences the severity of experimental autoimmune encephalomyelitis. 

In a rat experimental model of herpes simplex encephalitis, induced by HSV-1, the AF-16® peptide was used to suppress the raised ICP (Jennische, Bergström, Johansson et al, Brain Res, 2008; 1227: 189-197 link). The intranasal instillation of AF-16® resulted in a complete rescue of rats receiving 25 mcg twice daily from the fourth day after infection. The mortality rate in the untreated group was about 90%. AF-16® reduced the ICP increase and fluctuations and also abolished the pressure peaks in treated rats. 

Conclusions AF-16® and Brain inflammation

  • AF-16® rescues animals having lethal Herpes simplex encephalitis [bild 22]
  • AF-16® did not influence the virus multiplication or the virus distribution
  • AF-16® eliminates the signs of sickness mainly by reducing the abnormally raised intracranial pressure (ICP) 

AF-16® and Tumours

Many tumours are characterized by high interstitial fluid pressure (IFP). The increased IFP restricts the inflow and distribution of immune competent cells, nutrients, oxygene and drugs hampering the tumour treatment. 

The studies with AF-16® administered either locally in the tumour, intranasally or intravenously, show that it effectively and transiently decreases the raised tissue pressure in both the slowly and rapidly progressing tumours in experimental mammary tumours in rats (Al-Olama, Wallgren et al, The peptide AF-16® decreases the high interstitial fluid pressure and facilitates drug distribution in solid tumors, 2010, accepted for publication). 

The study showed that AF-16® increased the access of the cytotoxic drug doxorubicin in solid tumours as disclosed by increased number of intensely labeled nuclei.  A decrease of tumoural IFP could facilitate the inflow and distribution of cytotoxic drugs, such as doxorubicin, into the tumour tissue, and also increase the efficacy of radiation therapy due to increased oxygenation and hence improve tumour treatment. 

Conclusions AF-16® and Tumours

  • AF-16® reduces IFP in solid malignant tumours
  • AF-16® enables high molecular weight compounds, e.g. antibodies, to reach the target, tumour cells
  • AF-16® improves the blood circulation in tumours and the distribution within a tumour of low molecular weight drugs at chemotherapy
  • AF-16® increases oxygen tension in tumours, enhancing free radical formation at radiation 

Toxicological studies

The results from several toxicological studies with independent CRO and GLP standards have revealed that AF-16® has no toxicity or side effects. 

Overall conclusions for the AF-16® peptide

  • AF-16® offers therapeutic opportunities due to unique mode of action and very low toxicity

–        AF-16® counteracts elevated tissue pressures

–        AF-16® is neuroprotective

–        AF-16® likely to improve tumour therapy

–        AF-16® is beneficial in treating inflammation

  • No side effects